Scholars@Duke
Xiao-Fan Wang

Xiao-Fan Wang

Donald and Elizabeth Cooke Distinguished Professor of Cancer Research, in the School of Medicine
Pharmacology & Cancer Biology
wang0011@mc.duke.edu
Duke Box 3813, Durham, NC 27710
C218 Lev Sci Res Ctr, Durham, NC 27708

Scholarly Works - Journal articles

Single-cell and spatial detection of senescent cells using DeepScence.

Journal article Cell Genom · December 10, 2025 Accurately identifying senescent cells is essential for studying their spatial and molecular features. We developed DeepScence, a method based on deep neural networks, to identify senescent cells in single-cell and spatial transcriptomics data. DeepScence ... Full text Link to item Cite

WSTF nuclear autophagy regulates chronic but not acute inflammation.

Journal article Nature · August 2025 Acute inflammation is an essential response that our bodies use to combat infections1. However, in the absence of infections, chronic inflammation can have a pivotal role in the onset and progression of chronic diseases, such as arthritis, cancer, autoimmu ... Full text Open Access Link to item Cite

Single-cell and spatial detection of senescent cells using DeepScence.

Journal article bioRxiv · April 23, 2025 Accurately identifying senescent cells is essential for studying their spatial and molecular features. We developed DeepScence, a method based on deep neural networks, to identify senescent cells in single-cell and spatial transcriptomics data. DeepScence ... Full text Link to item Cite

Aberrant cytoplasmic expression of UHRF1 restrains the MHC-I-mediated anti-tumor immune response.

Journal article Nat Commun · October 3, 2024 Immunotherapy successfully complements traditional cancer treatment. However, primary and acquired resistance might limit efficacy. Reduced antigen presentation by MHC-I has been identified as potential resistance factor. Here we show that the epigenetic r ... Full text Open Access Link to item Cite

Breaking NGF-TrkA immunosuppression in melanoma sensitizes immunotherapy for durable memory T cell protection.

Journal article Nat Immunol · February 2024 Melanoma cells, deriving from neuroectodermal melanocytes, may exploit the nervous system's immune privilege for growth. Here we show that nerve growth factor (NGF) has both melanoma cell intrinsic and extrinsic immunosuppressive functions. Autocrine NGF e ... Full text Open Access Link to item Cite

Branched-Chain Amino Acid Accumulation Fuels the Senescence-Associated Secretory Phenotype.

Journal article Adv Sci (Weinh) · January 2024 The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine play critical roles in protein synthesis and energy metabolism. Despite their widespread use as nutritional supplements, BCAAs' full effects on mammalian physiology remain unc ... Full text Open Access Link to item Cite

Targeting senescent hepatocytes using the thrombomodulin-PAR1 inhibitor vorapaxar ameliorates NAFLD progression.

Journal article Hepatology · October 1, 2023 BACKGROUND AND AIMS: Senescent hepatocytes accumulate in parallel with fibrosis progression during NASH. The mechanisms that enable progressive expansion of nonreplicating cell populations and the significance of that process in determining NASH outcomes a ... Full text Open Access Link to item Cite

ATR inhibition induces synthetic lethality in mismatch repair-deficient cells and augments immunotherapy.

Journal article Genes Dev · October 1, 2023 The mismatch repair (MMR) deficiency of cancer cells drives mutagenesis and offers a useful biomarker for immunotherapy. However, many MMR-deficient (MMR-d) tumors do not respond to immunotherapy, highlighting the need for alternative approaches to target ... Full text Open Access Link to item Cite

Antagonizing the irreversible thrombomodulin-initiated proteolytic signaling alleviates age-related liver fibrosis via senescent cell killing.

Journal article Cell Res · July 2023 Cellular senescence is a stress-induced, stable cell cycle arrest phenotype which generates a pro-inflammatory microenvironment, leading to chronic inflammation and age-associated diseases. Determining the fundamental molecular pathways driving senescence ... Full text Open Access Link to item Cite

GABAergic signaling beyond synapses: an emerging target for cancer therapy.

Journal article Trends Cell Biol · May 2023 Traditionally, γ-aminobutyric acid (GABA) is best known for its role as a primary inhibitory neurotransmitter reducing neuronal excitability in the mammalian central nervous system (CNS), thereby producing calming effects. However, an emerging body of data ... Full text Open Access Link to item Cite

PPDPF Promotes the Development of Mutant KRAS-Driven Pancreatic Ductal Adenocarcinoma by Regulating the GEF Activity of SOS1.

Journal article Adv Sci (Weinh) · January 2023 The guanine nucleotide exchange factor (GEF) SOS1 catalyzes the exchange of GDP for GTP on RAS. However, regulation of the GEF activity remains elusive. Here, the authors report that PPDPF functions as an important regulator of SOS1. The expression of PPDP ... Full text Open Access Link to item Cite

Parkin coordinates mitochondrial lipid remodeling to execute mitophagy.

Journal article EMBO Rep · December 6, 2022 Autophagy has emerged as the prime machinery for implementing organelle quality control. In the context of mitophagy, the ubiquitin E3 ligase Parkin tags impaired mitochondria with ubiquitin to activate autophagic degradation. Although ubiquitination is es ... Full text Open Access Link to item Cite

Patient-derived organoids (PDOs) and PDO-derived xenografts (PDOXs): New opportunities in establishing faithful pre-clinical cancer models.

Journal article J Natl Cancer Cent · December 2022 One of the major bottlenecks in advancing basic cancer research and developing novel cancer therapies is the lack of in vitro pre-clinical models that faithfully recapitulate tumor properties in the patients. Monolayer cultures of cancer cell lines usually ... Full text Open Access Link to item Cite

Tumor-induced erythroid precursor-differentiated myeloid cells mediate immunosuppression and curtail anti-PD-1/PD-L1 treatment efficacy.

Journal article Cancer Cell · June 13, 2022 Despite the unprecedented success of immune checkpoint inhibitors (ICIs) as anti-cancer therapy, it remains a prevailing clinical need to identify additional mechanisms underlying ICI therapeutic efficacy and potential drug resistance. Here, using lineage ... Full text Link to item Cite

Cancer-cell-derived GABA promotes β-catenin-mediated tumour growth and immunosuppression.

Journal article Nat Cell Biol · February 2022 Many cancers have an unusual dependence on glutamine. However, most previous studies have focused on the contribution of glutamine to metabolic building blocks and the energy supply. Here, we report that cancer cells with aberrant expression of glutamate d ... Full text Open Access Link to item Cite

PPDPF alleviates hepatic steatosis through inhibition of mTOR signaling.

Journal article Nat Commun · May 24, 2021 Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease in the world, however, no drug treatment has been approved for this disease. Thus, it is urgent to find effective therapeutic targets for clinical intervention. I ... Full text Link to item Cite

Resident memory T cells in tumor-distant tissues fortify against metastasis formation.

Journal article Cell Rep · May 11, 2021 As a critical machinery for rapid pathogen removal, resident memory T cells (TRMs) are locally generated after the initial encounter. However, their development accompanying tumorigenesis remains elusive. Using a murine breast cancer model, we show that TR ... Full text Link to item Cite

TCR repertoire characteristics predict clinical response to adoptive CTL therapy against nasopharyngeal carcinoma.

Journal article Oncoimmunology · 2021 The past decade has witnessed the gradual and steady progress of adoptive T cell therapy in treating various types of cancer. In combination with gemcitabine and carboplatin chemotherapy, we previously conducted a clinical trial, NCT00690872, to treat Epst ... Full text Link to item Cite

Cellular senescence: from anti-cancer weapon to anti-aging target.

Journal article Sci China Life Sci · March 2020 Cellular senescence (CS) is a state of stable cell cycle arrest characterized by the production and secretion of inflammatory molecules. Early studies described oncogene-induced senescence (OIS) as a barrier to tumorigenesis, such that the therapeutic indu ... Full text Link to item Cite

BMP10 suppresses hepatocellular carcinoma progression via PTPRS-STAT3 axis.

Journal article Oncogene · November 2019 Bone morphogenetic protein 10 (BMP10), one member of the BMP family, is involved in various development events. Dysregulation of BMP10 has been observed in several diseases, including hypertensive cardiac hypertrophy, Hirschsprung disease and blood vessel ... Full text Link to item Cite

CHML promotes liver cancer metastasis by facilitating Rab14 recycle.

Journal article Nat Commun · June 7, 2019 Metastasis-associated recurrence is the major cause of poor prognosis in hepatocellular carcinoma (HCC), however, the underlying mechanisms remain largely elusive. In this study, we report that expression of choroideremia-like (CHML) is increased in HCC, a ... Full text Link to item Cite

Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians.

Journal article Genome Res · November 2018 Centenarians (CENs) are excellent subjects to study the mechanisms of human longevity and healthy aging. Here, we analyzed the transcriptomes of 76 centenarians, 54 centenarian-children, and 41 spouses of centenarian-children by RNA sequencing and found th ... Full text Link to item Cite

Synthetic lethality between HER2 and transaldolase in intrinsically resistant HER2-positive breast cancers.

Journal article Nat Commun · October 15, 2018 Intrinsic resistance to anti-HER2 therapy in breast cancer remains an obstacle in the clinic, limiting its efficacy. However, the biological basis for intrinsic resistance is poorly understood. Here we performed a CRISPR/Cas9-mediated loss-of-function gene ... Full text Open Access Link to item Cite

Switching off IMMP2L signaling drives senescence via simultaneous metabolic alteration and blockage of cell death.

Journal article Cell Res · June 2018 Cellular senescence is a fundamental cell fate playing a significant role throughout the natural aging process. However, the molecular determinants distinguishing senescence from other cell-cycle arrest states such as quiescence and post-mitotic state, and ... Full text Link to item Cite

CD36 initiates the secretory phenotype during the establishment of cellular senescence.

Journal article EMBO Rep · June 2018 Cellular senescence is a unique cell fate characterized by stable proliferative arrest and the extensive production and secretion of various inflammatory proteins, a phenomenon known as the senescence-associated secretory phenotype (SASP). The molecular me ... Full text Link to item Cite

Chemerin suppresses hepatocellular carcinoma metastasis through CMKLR1-PTEN-Akt axis.

Journal article Br J Cancer · May 2018 BACKGROUND: Chemerin, a known chemoattractant, participates in multiple biological events. However, its role in cancer remains largely unknown. METHODS: Chemerin expression was evaluated by real-time PCR, western blot and immunohistochemistry. Forced expre ... Full text Link to item Cite

Cilia loss sensitizes cells to transformation by activating the mevalonate pathway.

Journal article J Exp Med · January 2, 2018 Although cilia loss and cell transformation are frequently observed in the early stage of tumorigenesis, the roles of cilia in cell transformation are unknown. In this study, disrupted ciliogenesis was observed in cancer cells and pancreatic cancer tissues ... Full text Link to item Cite

TGF-β Family Signaling in the Control of Cell Proliferation and Survival.

Journal article Cold Spring Harb Perspect Biol · April 3, 2017 The transforming growth factor β (TGF-β) family controls many fundamental aspects of cellular behavior. With advances in the molecular details of the TGF-β signaling cascade and its cross talk with other signaling pathways, we now have a more coherent unde ... Full text Link to item Cite

Distinct Receptor Tyrosine Kinase Subsets Mediate Anti-HER2 Drug Resistance in Breast Cancer.

Journal article J Biol Chem · January 13, 2017 Targeted inhibitors of the human epidermal growth factor receptor 2 (HER2), such as trastuzumab and lapatinib, are among the first examples of molecularly targeted cancer therapy and have proven largely effective for the treatment of HER2-positive breast c ... Full text Open Access Link to item Cite

UHRF1 is required for basal stem cell proliferation in response to airway injury.

Journal article Cell Discov · 2017 Cellular senescence is a cell fate characterized by an irreversible cell cycle arrest, but the molecular mechanism underlying this senescence hallmark remains poorly understood. Through an unbiased search for novel senescence regulators in airway basal cel ... Full text Open Access Link to item Cite

Carcinogen 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis is accelerated in Smad3 heterozygous mice compared to Smad3 wild type mice.

Journal article Oncotarget · October 4, 2016 Previous studies based on cell culture and xenograft animal models suggest that Smad3 has tumor suppressor function for breast cancer during early stages of tumorigenesis. In this report, we show that DMBA (7,12-dimethylbenz[a]anthracene), a chemical carci ... Full text Link to item Cite

The histone deacetylase inhibitor trichostatin a decreases lymphangiogenesis by inducing apoptosis and cell cycle arrest via p21-dependent pathways.

Journal article BMC Cancer · September 30, 2016 BACKGROUND: The formation of new lymphatic vessels provides an additional route for tumour cells to metastasize. Therefore, inhibiting lymphangiogenesis represents an interesting target in cancer therapy. First evidence suggests that histone deacetylase in ... Full text Link to item Cite

Iron overload in hereditary tyrosinemia type 1 induces liver injury through the Sp1/Tfr2/hepcidin axis.

Journal article J Hepatol · July 2016 BACKGROUND & AIMS: Iron is an essential metal for fundamental metabolic processes, but little is known regarding the involvement of iron in other nutritional disorders. In the present study, we investigated disordered iron metabolism in a murine model of h ... Full text Link to item Cite

Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes.

Journal article Cancer Res · April 15, 2016 Chronic inflammation in liver tissue is an underlying cause of hepatocellular carcinoma. High levels of inflammatory cytokine IL18 in the circulation of patients with hepatocellular carcinoma correlates with poor prognosis. However, conflicting results hav ... Full text Link to item Cite

MiR-148a functions to suppress metastasis and serves as a prognostic indicator in triple-negative breast cancer.

Journal article Oncotarget · April 12, 2016 Triple-negative breast cancer (TNBC) presents a major challenge in the clinic due to its lack of reliable prognostic markers and targeted therapies. Accumulating evidence strongly supports the notion that microRNAs (miRNAs) are involved in tumorigenesis an ... Full text Link to item Cite

Dimethylfumarate effectively inhibits lymphangiogenesis via p21 induction and G1 cell cycle arrest.

Journal article Exp Dermatol · March 2016 Different pathologies, such as lymphoedema, cancer or psoriasis, are associated with abnormal lymphatic vessel formation. Therefore, influencing lymphangiogenesis is an interesting target. Recent evidence suggests that dimethylfumarate (DMF), an antipsoria ... Full text Link to item Cite

MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B.

Journal article Cancer Cell · January 11, 2016 The hypoxic tumor microenvironment serves as a niche for maintaining the glioma-initiating cells (GICs) that are critical for glioblastoma (GBM) occurrence and recurrence. Here, we report that hypoxia-induced miR-215 is vital for reprograming GICs to fit t ... Full text Open Access Link to item Cite

TGF-β-Regulated MicroRNAs and Their Function in Cancer Biology.

Journal article Methods Mol Biol · 2016 The transforming growth factor-β (TGF-β) is known to regulate a large number of biological processes and is involved in various aspects of tumor development. Recent studies have shown that the biogenesis of miRNAs can be regulated by TGF-β signaling direct ... Full text Link to item Cite

Noncoding RNAs Regulating Cancer Signaling Network.

Journal article Adv Exp Med Biol · 2016 The cellular signaling network plays a fundamental role during development and disease, especially cancer progression. By deregulating signaling pathways, cancer cells acquire hallmarks of the disease including uncontrolled proliferation, evasion from cell ... Full text Link to item Cite

Isolation of Glioma-Initiating Cells for Biological Study.

Journal article Adv Exp Med Biol · 2016 Glioblastoma multiforme (GBM, WHO grade IV astrocytoma) is the most common and lethal primary brain tumor in adults, with an average survival of slightly more than 1 year after initial diagnosis. GBMs display significant heterogeneity within the tumor mass ... Full text Link to item Cite

Smad3 Signaling Promotes Fibrosis While Preserving Cardiac and Aortic Geometry in Obese Diabetic Mice.

Journal article Circ Heart Fail · July 2015 BACKGROUND: Heart failure in diabetics is associated with cardiac hypertrophy, fibrosis and diastolic dysfunction. Activation of transforming growth factor-β/Smad3 signaling in the diabetic myocardium may mediate fibrosis and diastolic heart failure, while ... Full text Link to item Cite

A niche role for cancer exosomes in metastasis.

Journal article Nat Cell Biol · June 2015 Cancer cells are known to secrete exosomes with pro-metastatic effects. Pancreatic-cancer-derived exosomes are now shown to promote liver metastasis by eliciting pre-metastatic niche formation through a multi-step process. This involves uptake of exosome-d ... Full text Link to item Cite

Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies.

Journal article Front Med · June 2015 Drug resistance is a major factor that limits the efficacy of targeted cancer therapies. In this review, we discuss the main known mechanisms of resistance to receptor tyrosine kinase inhibitors, which are the most prevalent class of targeted therapeutic a ... Full text Link to item Cite

SMAD3 deficiency promotes vessel wall remodeling, collagen fiber reorganization and leukocyte infiltration in an inflammatory abdominal aortic aneurysm mouse model.

Journal article Sci Rep · May 18, 2015 TGF-β signaling plays critical roles in the pathogenesis of aneurysms; however, it is still unclear whether its role is protective or destructive. In this study, we investigate the role of SMAD3 in the pathogenesis of calcium chloride (CaCl2)-induced abdom ... Full text Link to item Cite

Inflammatory models drastically alter tumor growth and the immune microenvironment in hepatocellular carcinoma.

Journal article Sci Bull (Beijing) · April 1, 2015 Initiation and progression of hepatocellular carcinoma (HCC) is intimately associated with a chronically diseased liver tissue. This diseased liver tissue background is a drastically different microenvironment from the healthy liver, especially with regard ... Full text Link to item Cite

Post-transcriptional regulation of MTA family by microRNAs in the context of cancer.

Journal article Cancer Metastasis Rev · December 2014 MicroRNAs (miRNAs) are a class of 20-24 nt small non-coding RNAs that regulate a wide range of biological processes through changing the stability and translation of their target messenger RNA (mRNA) genes. Shortly after their identification, many miRNA ge ... Full text Link to item Cite

miR-33a promotes glioma-initiating cell self-renewal via PKA and NOTCH pathways.

Journal article J Clin Invest · October 2014 Glioblastoma (GBM) is the most common and lethal brain tumor in adults. Glioma-initiating cells (GICs) are stem-like cells that have been implicated in glioblastoma progression and recurrence; however, the distinct properties of GICs and non-GICs within GB ... Full text Link to item Cite

The hepatitis B virus-associated tumor microenvironment in hepatocellular carcinoma.

Journal article Natl Sci Rev · July 14, 2014 In contrast to a majority of cancer types, the initiation of hepatocellular carcinoma (HCC) is intimately associated with a chronically diseased liver tissue, with one of the most prevalent etiological factors being hepatitis B virus (HBV). Transformation ... Full text Link to item Cite

Rad17 recruits the MRE11-RAD50-NBS1 complex to regulate the cellular response to DNA double-strand breaks.

Journal article EMBO J · April 16, 2014 The MRE11-RAD50-NBS1 (MRN) complex is essential for the detection of DNA double-strand breaks (DSBs) and initiation of DNA damage signaling. Here, we show that Rad17, a replication checkpoint protein, is required for the early recruitment of the MRN comple ... Full text Link to item Cite

Microenvironmental regulation of cancer metastasis by miRNAs.

Journal article Trends Cell Biol · March 2014 miRNAs are a class of small, non-coding RNAs that regulate cancer progression, especially the processes of invasion and metastasis. Although earlier studies in metastasis primarily focused on the impact that miRNAs have on the intrinsic properties of cance ... Full text Link to item Cite

COUP-TFII and AKT are cancer targets pursued by SCBA award winners.

Journal article Cell Biosci · 2014 This thematic issue of Cell & Bioscience highlights review articles by Sophia Y. Tsai and Ming-Jer Tsai's research team on roles of COUP-TFII in tumor progression and metastasis and by Hui-Kuan Lin and his colleagues on posttranslational regulation of Akt ... Full text Link to item Cite

Differential effects of Smad3 targeting in a murine model of chronic kidney disease.

Journal article Physiol Rep · December 1, 2013 Transforming growth factor (TGF)-β1 has a pivotal role in the pathogenesis of progressive kidney diseases that are characterized by fibrosis. The main intracellular signaling pathway of TGF-β1 is the Smad system, where Smad2 and Smad3 play a central role i ... Full text Link to item Cite

A P(E)RM(I)T for BMP signaling.

Journal article Mol Cell · July 11, 2013 In this issue, Xu et al. (2013) report their interesting discovery of a critical step for initiating BMP signal transduction that requires arginine methylation at the plasma membrane. ... Full text Link to item Cite

miR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis.

Journal article Nat Cell Biol · March 2013 The tumour stroma is an active participant during cancer progression. Stromal cells promote tumour progression and metastasis through multiple mechanisms including enhancing tumour invasiveness and angiogenesis, and suppressing immune surveillance. We repo ... Full text Link to item Cite

A PK2/Bv8/PROK2 antagonist suppresses tumorigenic processes by inhibiting angiogenesis in glioma and blocking myeloid cell infiltration in pancreatic cancer.

Journal article PLoS One · 2013 Infiltration of myeloid cells in the tumor microenvironment is often associated with enhanced angiogenesis and tumor progression, resulting in poor prognosis in many types of cancer. The polypeptide chemokine PK2 (Bv8, PROK2) has been shown to regulate mye ... Full text Link to item Cite

A mediator lost in the war on cancer.

Journal article Cell · November 21, 2012 An unexpected role for a Mediator subunit, MED12, in resistance to multiple anticancer agents is revealed by Huang et al. Loss of MED12 confers drug resistance by activating transforming growth factor b (TGF-b) signaling. Inhibition of the TGF-b pathway re ... Full text Link to item Cite

A pentapeptide monocyte locomotion inhibitory factor protects brain ischemia injury by targeting the eEF1A1/endothelial nitric oxide synthase pathway.

Journal article Stroke · October 2012 BACKGROUND AND PURPOSE: Ischemic stroke is a major cause of death worldwide but lacks viable treatment or treatment targets. Monocyte locomotion inhibitory factor (MLIF) is a small heat-stable pentapeptide produced by Entamoeba histolytica in axenic cultur ... Full text Link to item Cite

TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma.

Journal article Cancer Cell · September 11, 2012 Portal vein tumor thrombus (PVTT) is strongly correlated to a poor prognosis for patients with hepatocellular carcinoma (HCC). In this study, we uncovered a causative link between hepatitis B virus (HBV) infection and development of PVTT. Mechanistically, ... Full text Link to item Cite

New secrets behind bone metastasis.

Journal article Cell Res · September 2012 Secreted proteins play essential roles in every step of cancer metastasis, while the identities and functions of those that contribute to tissue-specific metastasis are largely uncharacterized. Two articles in Cell Research report the discovery and functio ... Full text Link to item Cite

Bat3 facilitates H3K79 dimethylation by DOT1L and promotes DNA damage-induced 53BP1 foci at G1/G2 cell-cycle phases.

Journal article EMBO J · May 2, 2012 The methyltransferase DOT1L methylates histone H3 at K79 to facilitate specific biological events. H3K79 dimethylation (H3K79-2Me) by DOT1L influences the DNA damage response by promoting 53BP1 recruitment to DNA damage sites; however, it is unclear if thi ... Full text Link to item Cite

Where PI3K/Akt meets Smads: the crosstalk determines human embryonic stem cell fate.

Journal article Cell Stem Cell · March 2, 2012 Coordinated interactions between signaling networks govern the balance of cell fate decisions in human embryonic stem cells. In this issue, Singh et al. (2012) report that PI3K/Akt signaling switches Activin/Smad activity between pro-self-renewal and prodi ... Full text Link to item Cite

A novel, non-apoptotic role for Scythe/BAT3: a functional switch between the pro- and anti-proliferative roles of p21 during the cell cycle.

Journal article PLoS One · 2012 BACKGROUND: Scythe/BAT3 is a member of the BAG protein family whose role in apoptosis has been extensively studied. However, since the developmental defects observed in Bat3-null mouse embryos cannot be explained solely by defects in apoptosis, we investig ... Full text Link to item Cite

Dopamine and α-synuclein dysfunction in Smad3 null mice.

Journal article Molecular neurodegeneration · December 1, 2011 Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration in the substantia nigra (SN). Transforming growth factor-β1 (TGF-β1) levels increase in patients with PD, although the effects of this increment remain unclear. We have examined th ... Cite

Dopamine and α-synuclein dysfunction in Smad3 null mice.

Journal article Mol Neurodegener · October 13, 2011 BACKGROUND: Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration in the substantia nigra (SN). Transforming growth factor-β1 (TGF-β1) levels increase in patients with PD, although the effects of this increment remain unclear. We have ... Full text Link to item Cite

Trefoil factor 1 acts to suppress senescence induced by oncogene activation during the cellular transformation process.

Journal article Proc Natl Acad Sci U S A · April 19, 2011 Senescence is a cellular stress response characterized by persistent cell growth arrest under various stress conditions, including oncogene activation or tumor suppressor loss, which functions as a critical barrier that must be overcome to allow the progre ... Full text Link to item Cite

Abstract 2482: Bat3 facilitates histone H3 lysine 79 dimethylation by DOT1L to promote ionizing radiation-induced 53BP1 foci formation during G1- and G2-phases of the cell cycle

Journal article Cancer Research · April 15, 2011 AbstractDOT1L is a unique histone methyltransferase involved in normal cellular metabolism and in the initiation of certain leukemias. DOT1L specifically methylates histone H3 at K79, promoting the interacti ... Full text Cite

Abstract 3311: IL6-Stat3 signaling promotes glioma stem cell (GSC) survival under hypoxia environment through inhibition of cell-death inducing gene Bnip3

Journal article Cancer Research · April 15, 2011 AbstractGlioblastomas (GBMs) are the most common and lethal brain tumor in adults. In rapid-growing tumors like malignant glioma, hypoxia is an unavoidable condition even with aggressive angiogenesis. Recent ... Full text Cite

Sorafenib suppresses postsurgical recurrence and metastasis of hepatocellular carcinoma in an orthotopic mouse model.

Journal article Hepatology · February 2011 UNLABELLED: Surgical resection is the first-line treatment for hepatocellular carcinoma (HCC) patients with well-preserved liver function. Nevertheless, the rate of postoperative recurrence at 5 years is as high as 70%, and this gravely jeopardizes the the ... Full text Link to item Cite

Genome variation in Cryptococcus gattii, an emerging pathogen of immunocompetent hosts.

Journal article mBio · 2011 Cryptococcus gattii recently emerged as the causative agent of cryptococcosis in healthy individuals in western North America, despite previous characterization of the fungus as a pathogen in tropical or subtropical regions. As a foundation to study the ge ... Full text Link to item Cite

Tumor initiating cells in esophageal squamous cell carcinomas express high levels of CD44.

Journal article PLoS One · 2011 BACKGROUND: Esophageal Squamous Cell Carcinoma (ESCC) is a major subtype of esophageal cancer causing significant morbility and mortality in Asia. Mechanism of initiation and progression of this disease is unclear. Tumor initiating cells (TICs) are the sub ... Full text Link to item Cite

Smad3 signaling critically regulates fibroblast phenotype and function in healing myocardial infarction.

Journal article Circ Res · August 6, 2010 RATIONALE: Cardiac fibroblasts are key effector cells in the pathogenesis of cardiac fibrosis. Transforming growth factor (TGF)-beta/Smad3 signaling is activated in the border zone of healing infarcts and induces fibrotic remodeling of the infarcted ventri ... Full text Link to item Cite

Proteolysis of Rad17 by Cdh1/APC regulates checkpoint termination and recovery from genotoxic stress.

Journal article EMBO J · May 19, 2010 Recent studies have shown a critical function for the ubiquitin-proteasome system (UPS) in regulating the signalling network for DNA damage responses and DNA repair. To search for new UPS targets in the DNA damage signalling pathway, we have carried out a ... Full text Link to item Cite

Liver cancer: EphrinA2 promotes tumorigenicity through Rac1/Akt/NF-kappaB signaling pathway.

Journal article Hepatology · February 2010 UNLABELLED: Eph/Ephrin family, one of the largest receptor tyrosine kinase families, has been extensively studied in morphogenesis and neural development. Recently, growing attention has been paid to its role in the initiation and progression of various ca ... Full text Link to item Cite

Notch promotes radioresistance of glioma stem cells.

Journal article Stem Cells · January 2010 Radiotherapy represents the most effective nonsurgical treatments for gliomas. However, gliomas are highly radioresistant and recurrence is nearly universal. Results from our laboratory and other groups suggest that cancer stem cells contribute to radiores ... Full text Link to item Cite

Finale: the last minutes of Smads.

Journal article Cell · November 13, 2009 TGF-beta ligands induce phosphorylation of receptor-activated Smads at both the C-terminal tail and the linker region. Two papers from Massagué and colleagues (Alarcón et al., 2009; Gao et al., 2009) reveal a dual role for this linker phosphorylation, whic ... Full text Link to item Cite

Protein phosphatase 2A-dependent dephosphorylation of replication protein A is required for the repair of DNA breaks induced by replication stress.

Journal article Mol Cell Biol · November 2009 Eukaryotic genomic integrity is safeguarded by cell cycle checkpoints and DNA repair pathways, collectively known as the DNA damage response, wherein replication protein A (RPA) is a key regulator playing multiple critical roles. The genotoxic insult-induc ... Full text Link to item Cite

Targeting interleukin 6 signaling suppresses glioma stem cell survival and tumor growth.

Journal article Stem Cells · October 2009 Glioblastomas are the most common and most lethal primary brain tumor. Recent studies implicate an important role for a restricted population of neoplastic cells (glioma stem cells (GSCs)) in glioma maintenance and recurrence. We now demonstrate that GSCs ... Full text Link to item Cite

From breast to the brain: unraveling the puzzle of metastasis organotropism.

Journal article J Mol Cell Biol · October 2009 Metastatic colonization of different target organs is a highly selective process that depends on specialized properties of tumor cells. In a recent Nature paper, Massagué and colleagues built on their earlier success in functional genomic analysis of breas ... Full text Link to item Cite

NDRG4 is required for cell cycle progression and survival in glioblastoma cells.

Journal article J Biol Chem · September 11, 2009 NDRG4 is a largely unstudied member of the predominantly tumor suppressive N-Myc downstream-regulated gene (NDRG) family. Unlike its family members NDRG1-3, which are ubiquitously expressed, NDRG4 is expressed almost exclusively in the heart and brain. Giv ... Full text Link to item Cite

Reduced ATR or Chk1 expression leads to chromosome instability and chemosensitization of mismatch repair-deficient colorectal cancer cells.

Journal article Mol Biol Cell · September 2009 Genomic instability in colorectal cancer is categorized into two distinct classes: chromosome instability (CIN) and microsatellite instability (MSI). MSI is the result of mutations in the mismatch repair (MMR) machinery, whereas CIN is often thought to be ... Full text Link to item Cite

TGFbeta-stimulated Smad1/5 phosphorylation requires the ALK5 L45 loop and mediates the pro-migratory TGFbeta switch.

Journal article EMBO J · January 21, 2009 During the course of breast cancer progression, normally dormant tumour-promoting effects of transforming growth factor beta (TGFbeta), including migration, invasion, and metastasis are unmasked. In an effort to identify mechanisms that regulate the pro-mi ... Full text Link to item Cite

A special issue on TGF-beta signaling.

Journal article Cell Res · January 2009 Full text Link to item Cite

Signaling cross-talk between TGF-beta/BMP and other pathways.

Journal article Cell Res · January 2009 Transforming growth factor-beta (TGF-beta)/bone morphogenic protein (BMP) signaling is involved in the vast majority of cellular processes and is fundamentally important during the entire life of all metazoans. Deregulation of TGF-beta/BMP activity almost ... Full text Link to item Cite

Ligand-dependent ubiquitination of Smad3 is regulated by casein kinase 1 gamma 2, an inhibitor of TGF-beta signaling.

Journal article Oncogene · December 11, 2008 Transforming growth factor-beta (TGF-beta) elicits a variety of cellular activities primarily through a signaling cascade mediated by two key transcription factors, Smad2 and Smad3. Numerous regulatory mechanisms exist to control the activity of Smad3, the ... Full text Link to item Cite

The cytoplasmic deacetylase HDAC6 is required for efficient oncogenic tumorigenesis.

Journal article Cancer Res · September 15, 2008 Histone deacetylase inhibitors (HDACI) are promising antitumor agents. Although transcriptional deregulation is thought to be the main mechanism underlying their therapeutic effects, the exact mechanism and targets by which HDACIs achieve their antitumor e ... Full text Link to item Cite

In vitro assays for the extracellular matrix protein-regulated extravasation process.

Journal article CSH Protoc · August 1, 2008 INTRODUCTIONExtravasation, the process by which circulating tumor cells pass through the blood vessel wall, is a critical step of metastasis. Extracellular matrix (ECM) proteins secreted by the cancer cells are likely to play an interactive role in the dyn ... Full text Link to item Cite

Aven-dependent activation of ATM following DNA damage.

Journal article Curr Biol · July 8, 2008 BACKGROUND: In response to DNA damage, cells undergo either cell-cycle arrest or apoptosis, depending on the extent of damage and the cell's capacity for DNA repair. Cell-cycle arrest induced by double-stranded DNA breaks depends on activation of the ataxi ... Full text Link to item Cite

Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation.

Journal article Genes Dev · February 1, 2008 Metastasis, the major cause of cancer death, is a multistep process that requires interactions between cancer cells and stromal cells and between cancer cells and extracellular matrix. Molecular alterations of the extracellular matrix in the tumor microenv ... Full text Link to item Cite

Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling.

Journal article Genes Dev · January 1, 2008 The broad range of biological responses elicited by transforming growth factor-beta (TGF-beta) in various types of tissues and cells is mainly determined by the expression level and activity of the effector proteins Smad2 and Smad3. It is not fully underst ... Full text Link to item Cite

Essential role of Smad3 in infarct healing and in the pathogenesis of cardiac remodeling.

Journal article Circulation · November 6, 2007 BACKGROUND: Postinfarction cardiac repair is regulated through timely activation and repression of inflammatory pathways, followed by transition to fibrous tissue deposition and formation of a scar. The transforming growth factor-beta/Smad3 pathway is acti ... Full text Link to item Cite

Up-regulation of tumor susceptibility gene 101 conveys poor prognosis through suppression of p21 expression in ovarian cancer.

Journal article Clin Cancer Res · July 1, 2007 PURPOSE: The function of tumor susceptibility gene 101 (TSG101) in ovarian carcinogenesis is largely unexplored. The aim of this study is to investigate the role of TSG101 in human ovarian cancer development, to examine the expression levels of TSG101 in o ... Full text Link to item Cite

Role for the PP2A/B56delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis.

Journal article Cell · November 17, 2006 DNA-responsive checkpoints prevent cell-cycle progression following DNA damage or replication inhibition. The mitotic activator Cdc25 is suppressed by checkpoints through inhibitory phosphorylation at Ser287 (Xenopus numbering) and docking of 14-3-3. Ser28 ... Full text Link to item Cite

A phosphatase controls the fate of receptor-regulated Smads.

Journal article Cell · June 2, 2006 In this issue of Cell, Lin et al. (2006) answer one of the long-standing questions in the TGFbeta field by identifying a phosphatase, PPM1A, that directly dephosphorylates Smad2 and Smad3 to limit their activation. ... Full text Link to item Cite

Smad3-dependent nuclear translocation of beta-catenin is required for TGF-beta1-induced proliferation of bone marrow-derived adult human mesenchymal stem cells.

Journal article Genes Dev · March 15, 2006 Adult mesenchymal stem cells (MSCs) derived from bone marrow contribute to the regeneration of multiple types of mesenchymal tissues. Here we describe the functional role of a novel form of cross-talk between the transforming growth factor beta1 (TGF-beta1 ... Full text Link to item Cite

Loss of phosphatase and tensin homologue increases transforming growth factor beta-mediated invasion with enhanced SMAD3 transcriptional activity.

Journal article Cancer Res · December 15, 2005 In normal epithelial tissues, the multifunctional cytokine transforming growth factor-beta (TGF-beta) acts as a tumor suppressor through growth inhibition and induction of differentiation whereas in advanced cancers, TGF-beta promotes tumor progression thr ... Full text Link to item Cite

TLR agonists regulate PDGF-B production and cell proliferation through TGF-beta/type I IFN crosstalk.

Journal article EMBO J · December 7, 2005 Transforming growth factor-beta (TGF-beta) and type I interferon (IFN) autocrine/paracrine loops are recognized as key mediators of signaling cascades that control a variety of cellular functions. Here, we describe a novel mechanism by which Toll-like rece ... Full text Link to item Cite

Protein phosphatase 5 is required for ATR-mediated checkpoint activation.

Journal article Mol Cell Biol · November 2005 In response to DNA damage or replication stress, the protein kinase ATR is activated and subsequently transduces genotoxic signals to cell cycle control and DNA repair machinery through phosphorylation of a number of downstream substrates. Very little is k ... Full text Link to item Cite

Loss of Smad3-mediated negative regulation of Runx2 activity leads to an alteration in cell fate determination.

Journal article Mol Cell Biol · November 2005 Runx2 is required for osteoblast differentiation but is expressed in certain nonosteoblastic cells without activating the differentiation process, suggesting that its activity is suppressed through a lineage-specific mechanism. Here we report that primary ... Full text Link to item Cite

Stable RNA interference-mediated suppression of cyclophilin A diminishes non-small-cell lung tumor growth in vivo.

Journal article Cancer Res · October 1, 2005 Cyclophilin A (CypA) was recently reported to be overexpressed in non-small-cell lung cancer, and represents a potentially novel therapeutic target. To determine the role of CypA in oncogenesis, stable RNA interference (RNAi)-mediated knockdown of CypA was ... Full text Link to item Cite

Ubiquitin-mediated degradation a mechanism for fine-tuning TGF-beta signaling.

Journal article Cell · April 8, 2005 Effects of the cytokine TGF-beta can be dampened by E3 ubiquitin ligases that target specific Smads, the TGF-beta signal transducers, for proteolytic destruction. Two papers in this issue of Cell highlight the importance of this mechanism in regulating the ... Full text Link to item Cite

Human Rad9 is required for the activation of S-phase checkpoint and the maintenance of chromosomal stability.

Journal article Genes Cells · April 2005 In response to DNA damage or replication block, cells activate a battery of checkpoint signaling cascades to control cell cycle progression and elicit DNA repair in order to maintain genomic stability and integrity. Identified as a homolog of its fission y ... Full text Link to item Cite

Abnormal mouse lung alveolarization caused by Smad3 deficiency is a developmental antecedent of centrilobular emphysema.

Journal article Am J Physiol Lung Cell Mol Physiol · April 2005 Transforming growth factor-beta (TGF-beta) signaling plays an important regulatory role during lung development and remodeling. Smad3 is a major downstream signal transducer in the TGF-beta pathway from the cell membrane to the nucleus. In Smad3 null mutan ... Full text Link to item Cite

Combination therapy of inhibitors of epidermal growth factor receptor/vascular endothelial growth factor receptor 2 (AEE788) and the mammalian target of rapamycin (RAD001) offers improved glioblastoma tumor growth inhibition.

Journal article Mol Cancer Ther · January 2005 Malignant gliomas are highly lethal tumors that display striking genetic heterogeneity. Novel therapies that inhibit a single molecular target may slow tumor progression, but tumors are likely not dependent on a signal transduction pathway. Rather, maligna ... Link to item Cite

Secreted protein acidic, rich in cysteine (SPARC), mediates cellular survival of gliomas through AKT activation.

Journal article J Biol Chem · December 10, 2004 Secreted protein acidic, rich in cysteine (SPARC), is an extracellular matrix protein expressed in many advanced cancers, including malignant gliomas. We and others have previously shown that human glioma cell lines engineered to overexpress SPARC adopt an ... Full text Link to item Cite

ATR functions as a gene dosage-dependent tumor suppressor on a mismatch repair-deficient background.

Journal article EMBO J · August 4, 2004 The ataxia-telangiectasia mutated and rad3-related (ATR) kinase orchestrates cellular responses to DNA damage and replication stress. Complete loss of ATR function leads to chromosomal instability and cell death. However, heterozygous ATR mutations are fou ... Full text Link to item Cite

Casein kinase Iepsilon plays a functional role in the transforming growth factor-beta signaling pathway.

Journal article J Biol Chem · July 9, 2004 The transforming growth factor-beta (TGF-beta) signaling pathway is known to be involved in a wide range of biological events, including development, cellular differentiation, apoptosis, and oncogenesis. The TGF-beta signal is mediated by ligand binding to ... Full text Link to item Cite

SB-431542, a small molecule transforming growth factor-beta-receptor antagonist, inhibits human glioma cell line proliferation and motility.

Journal article Mol Cancer Ther · June 2004 Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that promotes malignant glioma invasion, angiogenesis, and immunosuppression. Antisense oligonucleotide suppression of TGF-beta(2) ligand expression has shown promise in preclinical a ... Link to item Cite

Activin induces hepatocyte cell growth arrest through induction of the cyclin-dependent kinase inhibitor p15INK4B and Sp1.

Journal article Cell Signal · June 2004 In this report, we examined the role of activin in the regulation of cell growth inhibition of human hepatocarcinoma cells. Using RNase protection assay for various cell cycle regulators and Western blotting experiments, we show that activin treatment of H ... Full text Link to item Cite

Acquired expression of periostin by human breast cancers promotes tumor angiogenesis through up-regulation of vascular endothelial growth factor receptor 2 expression.

Journal article Mol Cell Biol · May 2004 The late stages of human breast cancer development are poorly understood complex processes associated with the expression of genes by cancers that promote specific tumorigenic activities, such as angiogenesis. Here, we describe the identification of perios ... Full text Link to item Cite

Transforming growth factor-beta1 inhibition of vascular smooth muscle cell activation is mediated via Smad3.

Journal article J Biol Chem · April 16, 2004 Activation of vascular smooth muscle cells (VSMCs) by proinflammatory cytokines is a key feature of atherosclerotic lesion formation. Transforming growth factor (TGF)-beta1 is a pleiotropic growth factor that can modulate the inflammatory response in diver ... Full text Link to item Cite

Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway.

Journal article Cancer Cell · April 2004 Molecular mechanisms associated with tumor metastasis remain poorly understood. Here we report that acquired expression of periostin by colon cancer cells greatly promoted metastatic development of colon tumors. Periostin is overexpressed in more than 80% ... Full text Link to item Cite

Essential role for Smad3 in regulating MCP-1 expression and vascular inflammation.

Journal article Circ Res · March 19, 2004 Transforming growth factor (TGF)-beta(1) is a pleiotropic growth factor with known inhibitory effects on immune cell activation. However, the specific mechanism(s) and in vivo significance of the effectors of TGF-beta(1) modulation in the context of vascul ... Full text Link to item Cite

Transforming growth factor beta-mediated transcriptional repression of c-myc is dependent on direct binding of Smad3 to a novel repressive Smad binding element.

Journal article Mol Cell Biol · March 2004 Smad proteins are the most well-characterized intracellular effectors of the transforming growth factor beta (TGF-beta) signal. The ability of the Smads to act as transcriptional activators via TGF-beta-induced recruitment to Smad binding elements (SBE) wi ... Full text Link to item Cite

Requirement of protein phosphatase 5 in DNA-damage-induced ATM activation.

Journal article Genes Dev · February 1, 2004 The checkpoint kinase ATM is centrally involved in the cellular response to DNA double-strand breaks. However, the mechanism of ATM activation during genotoxic stress is only partially understood. Here we report a direct regulatory linkage between the prot ... Full text Link to item Cite

Transcriptional activation of p21(waf1/cip1) by alkylphospholipids: role of the mitogen-activated protein kinase pathway in the transactivation of the human p21(waf1/cip1) promoter by Sp1.

Journal article Cancer Res · January 15, 2004 Alkylphospholipids (ALKs) are a novel class of antitumor agents with an unknown mechanism of action. The first ALK tested in the clinic, miltefosine, has been approved recently in Europe for the local treatment of patients with cutaneous metastasis. Perifo ... Full text Link to item Cite

Human T-cell leukemia virus type 1 Tax activates cyclin-dependent kinase inhibitor p21/Waf1/Cip1 expression through a p53-independent mechanism: Inhibition of cdk2.

Journal article Int J Cancer · November 20, 2003 We investigated the possible involvement of HTLV-1 Tax in the transcriptional activation of p21/Waf1/Cip1 (hereafter p21), a potent inhibitor of cyclin-dependent kinases and cell growth. Tax transfection resulted in enhanced expression of p21 protein in T ... Full text Link to item Cite

Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling.

Journal article Science · September 5, 2003 beta-Arrestins bind to activated seven transmembrane-spanning (7TMS) receptors (G protein-coupled receptors) after the receptors are phosphorylated by G protein-coupled receptor kinases (GRKs), thereby regulating their signaling and internalization. Here, ... Full text Link to item Cite

Bone-related genes expressed in advanced malignancies induce invasion and metastasis in a genetically defined human cancer model.

Journal article J Biol Chem · May 2, 2003 We employed a genetically defined human cancer model to investigate the contributions of two genes up-regulated in several cancers to phenotypic changes associated with late stages of tumorigenesis. Specifically, tumor cells expressing two structurally unr ... Full text Link to item Cite

HIV-1 Vpr activates cell cycle inhibitor p21/Waf1/Cip1: a potential mechanism of G2/M cell cycle arrest.

Journal article Virology · January 20, 2003 The Vpr gene of human immunodeficiency virus type 1 (HIV-1) encodes a 14-kDa protein that prevents cell proliferation by causing arrest in the G2/M phase of the cell cycle. Here we report the first evidence that Vpr activates the expression and transcripti ... Full text Link to item Cite

Smads "freeze" when they ski.

Journal article Structure · December 2002 The transforming growth factor-beta (TGF-beta) signal is manifest through activated heteromeric Smad complex-mediated transcriptional modulation of target genes that translates into diverse, context-specific biologic effects, such as the potent TGF-beta-in ... Full text Link to item Cite

Transforming growth factor beta 1 dysregulation in a human oral carcinoma tumour progression model.

Journal article Cell Prolif · June 2002 A human oral tumour progression model was established that consists of normal epithelial cells and three cell lines representing stages from dysplastic to metastatic cells. To investigate the impact of exogenous transforming growth factor-beta 1 on this mo ... Full text Link to item Cite

HDAC6 is a microtubule-associated deacetylase.

Journal article Nature · May 23, 2002 Reversible acetylation of alpha-tubulin has been implicated in regulating microtubule stability and function. The distribution of acetylated alpha-tubulin is tightly controlled and stereotypic. Acetylated alpha-tubulin is most abundant in stable microtubul ... Full text Link to item Cite

Smad3 deficiency attenuates bleomycin-induced pulmonary fibrosis in mice.

Journal article Am J Physiol Lung Cell Mol Physiol · March 2002 Transforming growth factor-beta (TGF-beta) signaling plays an important regulatory role during lung fibrogenesis. Smad3 was identified in the pathway for transducing TGF-beta signals from the cell membrane to the nucleus. Using mice without Smad3 gene expr ... Full text Link to item Cite

The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis.

Journal article J Bone Miner Res · October 2001 Smad3 is a well-characterized intracellular effector of the transforming growth factor beta (TGF-beta) signaling pathway and was implicated recently in the potentiation of vitamin D receptor (VDR)-mediated signaling. Given that both TGF-beta and vitamin D ... Full text Link to item Cite

The role of Smad3 in mediating mouse hepatic stellate cell activation.

Journal article Hepatology · July 2001 Transforming growth factor beta (TGF-beta) is the most potent profibrogenic mediator in liver fibrosis. Although Smad proteins have been identified as intracellular mediators in the TGF-beta signaling pathway, the function of individual Smad proteins remai ... Full text Link to item Cite

An essential role for Mad homology domain 1 in the association of Smad3 with histone deacetylase activity*.

Journal article J Biol Chem · June 22, 2001 The Smads are a family of sequence-specific DNA-binding proteins that modulate transcription in response to transforming growth factor beta (TGFbeta) by recruiting transcriptional activators like the histone acetyltransferase, p300/CBP, or repressors like ... Full text Link to item Cite

ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses.

Journal article Nature · June 21, 2001 Genotoxic stress triggers the activation of checkpoints that delay cell-cycle progression to allow for DNA repair. Studies in fission yeast implicate members of the Rad family of checkpoint proteins, which includes Rad17, Rad1, Rad9 and Hus1, as key early- ... Full text Link to item Cite

The activity of guanine exchange factor NET1 is essential for transforming growth factor-beta-mediated stress fiber formation.

Journal article J Biol Chem · May 4, 2001 To examine signaling pathways underlying transforming growth factor-beta (TGF-beta)-mediated changes in cell morphology, we used a microarray system to identify downstream target genes that may play a role in this process. Through this approach, we found t ... Full text Link to item Cite

A genetically tractable model of human glioma formation.

Journal article Cancer Res · May 1, 2001 Gliomas remain one of the deadliest forms of cancer. Improved therapeutics will require a better understanding of the molecular nature of these tumors. We, therefore, mimicked the most common genetic changes found in grade III-IV gliomas, disruption of the ... Link to item Cite

Transforming growth factor-beta signaling in cancer.

Journal article Microsc Res Tech · February 15, 2001 Transforming growth factor (TGF-beta) is a multifunctional polypeptide implicated in the regulation of a variety of cellular processes including growth, differentiation, apoptosis, adhesion, and motility. Abnormal activation or inhibition of these TGF-beta ... Full text Link to item Cite

Acrylamide-regulated neurofilament expression in rat pheochromocytoma cells.

Journal article Brain Res · January 10, 2000 Using the rat pheochromocytoma cell line (PC12), we present molecular evidence that the neurotoxicant acrylamide directly induces neurofilament gene expression, and the signaling pathways are initially distinctive from, but eventually merged into, that for ... Full text Link to item Cite

The Smads: transcriptional regulation and mouse models.

Journal article Cytokine Growth Factor Rev · 2000 The field of transforming growth factor-beta (TGF-beta) signaling sees periodic discoveries that revolutionize our thinking, redirect our experiments, and peak our excitement. One of the first such discoveries was less than a decade ago: the molecular clon ... Full text Link to item Cite

The MEK pathway is required for stimulation of p21(WAF1/CIP1) by transforming growth factor-beta.

Journal article J Biol Chem · December 10, 1999 Transforming growth factor-beta (TGF-beta)can induce the cyclin-dependent kinase inhibitors p21 and p15 in a variety of cell types. We have shown previously that Smad3 is required for the growth inhibitory activity of TGF-beta, whereas overexpression of Sm ... Full text Link to item Cite

Transforming growth factor-beta-mediated p15(INK4B) induction and growth inhibition in astrocytes is SMAD3-dependent and a pathway prominently altered in human glioma cell lines.

Journal article J Biol Chem · December 3, 1999 We sought to characterize the pathway by which the multifunctional cytokine transforming growth factor-beta (TGF-beta) inhibits the proliferation of normal astrocytes, and we analyzed the alterations in the TGF-beta pathway in human glioma cell lines. Upon ... Full text Link to item Cite

c-Jun enhancement of cyclic adenosine 3',5'-monophosphate response element-dependent transcription induced by transforming growth factor-beta is independent of c-Jun binding to DNA.

Journal article Mol Endocrinol · December 1999 Transforming growth factor-beta (TGFbeta) enhances transcription from reporter genes regulated by a single consensus cAMP-response element (CRE) upon transfection into the immortalized human keratinocyte cell line, HaCaT. Whereas both CRE-binding protein ( ... Full text Link to item Cite

Ras induces p21Cip1/Waf1 cyclin kinase inhibitor transcriptionally through Sp1-binding sites.

Journal article Oncogene · November 4, 1999 p21Cip1/Waf1 cyclin-dependent kinase inhibitor (p21) is inducible by Raf and mitogen-activated protein kinase kinase (MAPKK), but the level of regulation is unknown. We show here by conditional and transient Ras-expression models that Ras induces p21. Indu ... Full text Link to item Cite

Cooperation of Sp1 and p300 in the induction of the CDK inhibitor p21WAF1/CIP1 during NGF-mediated neuronal differentiation.

Journal article Oncogene · May 6, 1999 Addition of nerve growth factor (NGF) to PC12 cells promotes neuronal differentiation while inhibiting cell proliferation. In order to understand how NGF exerts its antimitogenic effect during differentiation, we have studied the mechanism by which this fa ... Full text Link to item Cite

Smads bind directly to the Jun family of AP-1 transcription factors.

Journal article Proc Natl Acad Sci U S A · April 27, 1999 Smad3 and Smad4 are sequence-specific DNA-binding factors that bind to their consensus DNA-binding sites in response to transforming growth factor beta (TGFbeta) and activate transcription. Recent evidence implicates Smad3 and Smad4 in the transcriptional ... Full text Link to item Cite

UV radiation is a transcriptional inducer of p21(Cip1/Waf1) cyclin-kinase inhibitor in a p53-independent manner.

Journal article Exp Cell Res · April 10, 1999 p53 target genes p21(Cip1/Waf1) cyclin-kinase inhibitor (p21 CKI), GADD45, bax, and cyclin G and genes affecting the redox state of the cells are implicated in p53 damage control responses. In order to attribute their functions and dependency of p53 in UV- ... Full text Link to item Cite

Targeted disruption of Smad3 reveals an essential role in transforming growth factor beta-mediated signal transduction.

Journal article Mol Cell Biol · April 1999 The Smads are a family of nine related proteins which function as signaling intermediates for the transforming growth factor beta (TGF-beta) superfamily of ligands. To discern the in vivo functions of one of these Smads, Smad3, we generated mice harboring ... Full text Link to item Cite

Smad3-Smad4 and AP-1 complexes synergize in transcriptional activation of the c-Jun promoter by transforming growth factor beta.

Journal article Mol Cell Biol · March 1999 Transcriptional regulation by transforming growth factor beta (TGF-beta) is a complex process which is likely to involve cross talk between different DNA responsive elements and transcription factors to achieve maximal promoter activation and specificity. ... Full text Link to item Cite

TGF-beta-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein.

Journal article Mol Biol Cell · December 1998 Smads are intermediate effector proteins that transduce the TGF-beta signal from the plasma membrane to the nucleus, where they participate in transactivation of downstream target genes. We have shown previously that coactivators p300/CREB-binding protein ... Full text Link to item Cite

The mammalian Rad24 homologous to yeast Saccharomyces cerevisiae Rad24 and Schizosaccharomyces pombe Rad17 is involved in DNA damage checkpoint.

Journal article Cell Growth Differ · December 1998 Cell cycle checkpoint proteins play critical roles in maintaining genomic stability and integrity to prevent the development of cancer and hereditary diseases. Here we report the isolation of a novel mouse gene encoding the protein MmRad24 [MmRad24 is the ... Link to item Cite

Quantitive estimates of outcrossing rates in a natural population of Sagittaria potamogetifolia

Journal article Wuhan Daxue Xuebao Journal of Wuhan University · December 1, 1998 The outcrossing rates of two subpopulations in a population of Sagittaria potamogetifolia were estimated by sampling from natural habitats and using single genetic marker locus. The value of subpopulation I (t̄̂I = (81. 9 ± 24.1)%) is remarkably h ... Cite

Sp1, but not Sp3, functions to mediate promoter activation by TGF-beta through canonical Sp1 binding sites.

Journal article Nucleic Acids Res · May 15, 1998 Transforming growth factor beta (TGF-beta) causes growth arrest at the G1 phase of the cell cycle in most cell types. Both the cyclin dependent kinase inhibitor p15(INK4B) and p21(Cip1/WAF1) genes have been found to be induced by TGF-beta in human keratino ... Full text Link to item Cite

Inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase pathway induces p53-independent transcriptional regulation of p21(WAF1/CIP1) in human prostate carcinoma cells.

Journal article J Biol Chem · April 24, 1998 Progression through the cell cycle is controlled by the induction of cyclins and the activation of cognate cyclin-dependent kinases. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor lovastatin induces growth arrest and cell death in ... Full text Link to item Cite

FKBP12 is not required for the modulation of transforming growth factor beta receptor I signaling activity in embryonic fibroblasts and thymocytes.

Journal article Cell Growth Differ · March 1998 Transforming growth factor beta (TGF-beta) signals through a heteromeric complex of type I and type II transmembrane serine-threonine kinases. Recent evidence suggests that the immunophilin FKBP12 modulates the activity of the type I receptor, based on dat ... Link to item Cite

Transforming growth factor beta stimulates the human immunodeficiency virus 1 enhancer and requires NF-kappaB activity.

Journal article Mol Cell Biol · January 1998 Transforming growth factor beta (TGF-beta) is the prototype of a large superfamily of signaling molecules involved in the regulation of cell growth and differentiation. In certain patients infected with human immunodeficiency virus type 1 (HIV-1), increase ... Full text Link to item Cite

Tumor suppressor Smad4 is a transforming growth factor beta-inducible DNA binding protein.

Journal article Mol Cell Biol · December 1997 Members of the Smad family of proteins are thought to play important roles in transforming growth factor beta (TGF-beta)-mediated signal transduction. In response to TGF-beta, specific Smads become inducibly phosphorylated, form heteromers with Smad4, and ... Full text Link to item Cite

E2F4-RB and E2F4-p107 complexes suppress gene expression by transforming growth factor beta through E2F binding sites.

Journal article Proc Natl Acad Sci U S A · May 13, 1997 Transforming growth factor beta (TGF-beta) causes growth arrest in most cell types. TGF-beta induces hypophosphorylation of retinoblastoma susceptibility gene 1 product (RB), which sequesters E2F factors needed for progression into S phase of the cell cycl ... Full text Link to item Cite

Expression of transforming growth factor beta (TGFbeta) type III receptor restores autocrine TGFbeta1 activity in human breast cancer MCF-7 cells.

Journal article J Biol Chem · May 9, 1997 While transforming growth factor beta (TGFbeta) type III receptor (RIII) is known to increase TGFbeta1 binding to its type II receptor (RII), the significance of this phenomenon is not known. We used human breast cancer MCF-7 cells to study the role of RII ... Full text Link to item Cite

Smad5 induces ventral fates in Xenopus embryo.

Journal article Dev Biol · April 15, 1997 The Smad proteins have been implicated in the intracellular signaling of transforming growth factor-beta (TGF-beta) ligands. Here we describe the function of Smad5 in early Xenopus development. Misexpression of Smad5 in the embryo causes ventralization and ... Full text Link to item Cite

The viral oncoprotein E1A blocks transforming growth factor beta-mediated induction of p21/WAF1/Cip1 and p15/INK4B.

Journal article Mol Cell Biol · April 1997 The adenovirus early gene product E1A is a potent stimulator of cellular proliferation, which when overexpressed can overcome the growth-inhibitory effects of the polypeptide hormone transforming growth factor beta (TGF-beta). The ability of TGF-beta to ar ... Full text Link to item Cite

Expression of mRNAs coding for the transforming growth factor-beta receptors in brain regions of euthyroid and hypothyroid neonatal rats and in adult brain.

Journal article Brain Res Dev Brain Res · March 17, 1997 The TGF-beta family of peptides has been postulated to play a role in control of the cell cycle but also may act in the developing brain to influence neuronal differentiation and survival. Because reception of TGF-beta signals requires the simultaneous exp ... Full text Link to item Cite

The TGFβ receptors and signaling pathways

Journal article Growth Factors and Cytokines in Health and Disease · December 1, 1996 Full text Cite

Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth.

Journal article Proc Natl Acad Sci U S A · August 20, 1996 The dwarfin protein family has been genetically implicated in transforming growth factor beta (TGF-beta)-like signaling pathways in Drosophila and Caenorhabditis elegans. To investigate the role of these proteins in mammalian signaling pathways, we have is ... Full text Link to item Cite

Reduced expression of transforming growth factor beta type I receptor contributes to the malignancy of human colon carcinoma cells.

Journal article J Biol Chem · July 19, 1996 Transforming growth factor beta (TGFbeta) type I (RI) and type II (RII) receptors are essential for TGFbeta signal transduction. A human colon carcinoma cell line, designated GEO, is marginally responsive to TGFbeta and expresses a low level of RI mRNA rel ... Full text Link to item Cite

Signaling by the transforming growth factor-beta receptors.

Journal article Biochim Biophys Acta · December 18, 1995 Full text Link to item Cite

Functional analysis of the transforming growth factor beta responsive elements in the WAF1/Cip1/p21 promoter.

Journal article J Biol Chem · December 1, 1995 The transforming growth factor beta s (TGF-beta s) are a group of multifunctional growth factors that inhibit cell cycle progression in many cell types. The TGF-beta-induced cell cycle arrest has been partially attributed to the regulatory effects of TGF-b ... Full text Link to item Cite

Transforming growth factor beta activates the promoter of cyclin-dependent kinase inhibitor p15INK4B through an Sp1 consensus site.

Journal article J Biol Chem · November 10, 1995 Transforming growth factor beta (TGF-beta) causes growth arrest in the G1 phase in many cell types. One probable pathway for this growth inhibition is through the TGF-beta-mediated up-regulation of the cyclin-dependent kinase (CDK) inhibitor p15INK4B, whic ... Full text Link to item Cite

Demonstration that mutation of the type II transforming growth factor beta receptor inactivates its tumor suppressor activity in replication error-positive colon carcinoma cells.

Journal article J Biol Chem · September 15, 1995 Escape from negative growth regulation by transforming growth factor beta (TGF-beta) as a result of the loss of TGF-beta type II receptor (RII) expression has been found to be associated with the replication error (RER) colorectal cancer genotype, which is ... Full text Link to item Cite

Restricted expression of type-II TGF beta receptor in murine embryonic development suggests a central role in tissue modeling and CNS patterning.

Journal article Mech Dev · August 1995 The type-II TGF beta receptor mediates many of the biological responses to TGF beta. An examination of the expression of the type-II TGF beta receptor during mouse embryogenesis therefore provides specific information about the role of TGF beta during embr ... Full text Link to item Cite

Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism.

Journal article Proc Natl Acad Sci U S A · June 6, 1995 The transforming growth factor beta s (TGF-beta s) are a group of multifunctional growth factors which inhibit cell cycle progression in many cell types. The TGF-beta-induced cell cycle arrest has been partially attributed to the regulatory effects of TGF- ... Full text Link to item Cite

Expression of the E2F1 transcription factor overcomes type beta transforming growth factor-mediated growth suppression.

Journal article Proc Natl Acad Sci U S A · January 17, 1995 Inhibition of cell growth by type beta transforming growth factor (TGF-beta) occurs in mid-G1 and is associated with decreased G1 cyclin-dependent kinase activity and maintenance of the retinoblastoma tumor suppressor protein Rb in an underphosphorylated, ... Full text Link to item Cite

Expression of transforming growth factor beta type II receptor leads to reduced malignancy in human breast cancer MCF-7 cells.

Journal article J Biol Chem · October 21, 1994 The role of transforming growth factor (TGF) beta type II receptor in reversing the malignant phenotype of human breast cancer MCF-7 cells was examined. MCF-7 cells were insensitive to TGF beta 1 and expressed undetectable levels of cell surface TGF beta t ... Link to item Cite

A single heteromeric receptor complex is sufficient to mediate biological effects of transforming growth factor-beta ligands.

Journal article J Biol Chem · May 27, 1994 Transforming growth factor beta (TGF-beta), a multifunctional cytokine that regulates a variety of biological functions, signals through a heteromeric receptor complex of the type I and type II TGF-beta receptors. The type II receptor, a transmembrane seri ... Link to item Cite

A transforming growth factor beta type I receptor that signals to activate gene expression.

Journal article Science · January 7, 1994 Transforming growth factor beta (TGF-beta) is a multifunctional factor that regulates many aspects of cellular functions. TGF-beta signals through a heteromeric complex of the type I and type II TGF-beta receptors. However, the molecular mechanism of signa ... Full text Link to item Cite

TGF-β activates gene expression

Journal article Biomedicine and Pharmacotherapy · January 1, 1994 Full text Cite

Cloning and developmental expression of the chick type II and type III TGF beta receptors.

Journal article Dev Dyn · January 1994 To address the role of peptide growth factors in chick organogenesis, we have focused on TGF beta 2 and have cloned the chick Type II and Type III TGF beta receptors. The chick Type II receptor is a serine/threonine kinase with a ligand binding profile ide ... Full text Link to item Cite

TGF beta signals through a heteromeric protein kinase receptor complex.

Journal article Cell · December 11, 1992 Transforming growth factor beta (TGF beta) binds with high affinity to the type II receptor, a transmembrane protein with a cytoplasmic serine/threonine kinase domain. We show that the type II receptor requires both its kinase activity and association with ... Full text Link to item Cite

Expression cloning of TGF-beta receptors.

Journal article Mol Reprod Dev · June 1992 Using a powerful expression cloning method in COS cells, we have cloned the TGF-beta types II and III receptors. The type III TGF-beta receptor is a membrane-bound proteoglycan with a core protein of about 110 kDa. Stable expression of the type III recepto ... Full text Link to item Cite

Expression cloning of the TGF-beta type II receptor, a functional transmembrane serine/threonine kinase.

Journal article Cell · February 21, 1992 A cDNA encoding the TGF-beta type II receptor protein has been isolated by an expression cloning strategy. The cloned cDNA, when transfected into COS cells, leads to overexpression of an approximately 80 kd protein that specifically binds radioiodinated TG ... Full text Link to item Cite

Expression cloning and characterization of the TGF-beta type III receptor.

Journal article Cell · November 15, 1991 The rat TGF-beta type III receptor cDNA has been cloned by overexpression in COS cells. The encoded receptor is an 853 amino acid protein with a large N-terminal extracellular domain containing at least one site for glycosaminoglycan addition, a single hyd ... Full text Link to item Cite

In vivo functional analysis of in vitro protein binding sites in the immunoglobulin heavy chain enhancer.

Journal article Nucleic Acids Res · April 25, 1988 We have systematically investigated the functional role of protein binding sites within the mouse immunoglobulin heavy chain enhancer which we previously identified by in vitro binding studies (1,2). Each binding site was deleted, mutant enhancers were clo ... Full text Link to item Cite

Absence of TGF-beta receptors and growth inhibitory responses in retinoblastoma cells.

Journal article Science · April 8, 1988 The responses of retinoblastoma tumor cells and normal retinal cells to various growth inhibitory factors were examined. Whereas fetal retinal cells were highly sensitive to the antimitogenic effects of transforming growth factor beta 1 (TGF-beta 1), retin ... Full text Link to item Cite

Absence of TGF-β receptors and growth inhibitory responses in retinoblastoma cells

Journal article Science · 1988 The responses of retinoblastoma tumor cells and normal retinal cells to various growth inhibitory factors were examined. Whereas fetal retinal cells were highly sensitive to the antimitogenic effects of transforming growth factor β1 (TGF-β1), retinoblastom ... Cite

Deletions of a DNA sequence in retinoblastomas and mesenchymal tumors: organization of the sequence and its encoded protein.

Journal article Proc Natl Acad Sci U S A · December 1987 Retinoblastoma is a childhood tumor that can arise because of mutant alleles acquired as somatic or germinal mutations. The mutant allele can be carried in the germ line. The mutations creating these alleles act by inactivating copies of a recessive oncoge ... Full text Link to item Cite

SV40 enhancer-binding factors are required at the establishment but not the maintenance step of enhancer-dependent transcriptional activation.

Journal article Cell · October 24, 1986 We have used temperature-sensitive COS cells to design delayed competition experiments in which competition for simian virus 40 (SV40) enhancer factors occurs after enhancer-dependent transcription has been established. The results demonstrate that competi ... Full text Link to item Cite

The endogenous immunoglobulin heavy chain enhancer can activate tandem VH promoters separated by a large distance.

Journal article Cell · December 1985 The availability of a clone containing two linked immunoglobulin heavy chain variable region genes located 15.8 kb apart has allowed us to study the functional capabilities of the immunoglobulin heavy chain transcriptional enhancer element in its normal ch ... Full text Link to item Cite

Transcriptional enhancer elements in the mouse immunoglobulin heavy chain locus.

Journal article Science · August 12, 1983 Two regions in the immunoglobulin heavy chain locus were tested for their ability to enhance transcription of the SV40 early promoter. A portion of the intervening sequence between the heavy chain joining region (Jh) and the constant region of the mu chain ... Full text Link to item Cite