Scholars@Duke
Hui-Kuan Lin

Hui-Kuan Lin

Fred and Janet Sanfilippo Distinguished Professor
Pathology
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Selected Publications

Protocol to analyze the role of various metabolites in impacting global RNA 5-methylcytosine levels in cultured cells by dot blot.

Journal Article STAR Protoc · March 15, 2024 RNA 5-methylcytosine (m5C) modification critically impacts many biological processes. Here, we provide a protocol to analyze the role of various metabolites in impacting global RNA m5C levels in cultured cells by dot blot. We describe steps for treating cu ... Full text Link to item Cite

NSUN2 is a glucose sensor suppressing cGAS/STING to maintain tumorigenesis and immunotherapy resistance.

Journal Article Cell Metab · October 3, 2023 Glucose metabolism is known to orchestrate oncogenesis. Whether glucose serves as a signaling molecule directly regulating oncoprotein activity for tumorigenesis remains elusive. Here, we report that glucose is a cofactor binding to methyltransferase NSUN2 ... Full text Link to item Cite

Pyruvate dehydrogenase kinase supports macrophage NLRP3 inflammasome activation during acute inflammation.

Journal Article Cell Rep · January 31, 2023 Activating the macrophage NLRP3 inflammasome can promote excessive inflammation with severe cell and tissue damage and organ dysfunction. Here, we show that pharmacological or genetic inhibition of pyruvate dehydrogenase kinase (PDHK) significantly attenua ... Full text Open Access Link to item Cite

AMPK signaling and its targeting in cancer progression and treatment.

Journal Article Semin Cancer Biol · October 2022 The intrinsic mechanisms sensing the imbalance of energy in cells are pivotal for cell survival under various environmental insults. AMP-activated protein kinase (AMPK) serves as a central guardian maintaining energy homeostasis by orchestrating diverse ce ... Full text Link to item Cite

Identification of myo-inositol-binding proteins by using the biotin pull-down strategy in cultured cells.

Journal Article STAR Protoc · June 17, 2022 Metabolites are not only substrates in metabolic reactions, but they also serve as signaling molecules to regulate diverse biological functions. Identification of the binding proteins for the metabolites helps in the understanding of their functions beyond ... Full text Open Access Link to item Cite

The foundational framework of tumors: Gametogenesis, p53, and cancer

Journal Article Seminars in Cancer Biology · June 2022 Full text Cite

SIRPγ-expressing cancer stem-like cells promote immune escape of lung cancer via Hippo signaling.

Journal Article J Clin Invest · March 1, 2022 Cancer stem-like cells (CSLCs) acquire enhanced immune checkpoint responses to evade immune cell killing and promote tumor progression. Here we showed that signal regulatory protein γ (SIRPγ) determined CSLC properties and immune evasiveness in a small pop ... Full text Open Access Link to item Cite

Inositol serves as a natural inhibitor of mitochondrial fission by directly targeting AMPK.

Journal Article Mol Cell · September 16, 2021 Mitochondrial dynamics regulated by mitochondrial fusion and fission maintain mitochondrial functions, whose alterations underline various human diseases. Here, we show that inositol is a critical metabolite directly restricting AMPK-dependent mitochondria ... Full text Open Access Link to item Cite

Author Correction: SETDB1-mediated methylation of Akt promotes its K63-linked ubiquitination and activation leading to tumorigenesis.

Journal Article Nat Cell Biol · June 2021 A Correction to this paper has been published: https://doi.org/10.1038/s41556-021-00686-x. ... Full text Link to item Cite

AMPK maintains TCA cycle through sequential phosphorylation of PDHA to promote tumor metastasis

Journal Article Cell Stress · December 14, 2020 Cancer represents the leading public health problem throughout the world. Globally, about one out of six deaths is related to cancer, which is largely due to the metastatic lesions. However, there are no effective strategies for targeting cancer me ... Full text Cite

The Skp2 Pathway: A Critical Target for Cancer Therapy.

Journal Article Semin Cancer Biol · December 2020 Strictly regulated protein degradation by ubiquitin-proteasome system (UPS) is essential for various cellular processes whose dysregulation is linked to serious diseases including cancer. Skp2, a well characterized component of Skp2-SCF E3 ligase complex, ... Full text Open Access Link to item Cite

Phosphorylation of PDHA by AMPK Drives TCA Cycle to Promote Cancer Metastasis.

Journal Article Mol Cell · October 15, 2020 Cancer metastasis accounts for the major cause of cancer-related deaths. How disseminated cancer cells cope with hostile microenvironments in secondary site for full-blown metastasis is largely unknown. Here, we show that AMPK (AMP-activated protein kinase ... Full text Link to item Cite

Identification of primordial germ cell-like cells as liver metastasis initiating cells in mouse tumour models

Journal Article Cell Discovery · March 24, 2020 AbstractLiver metastasis, characterized by the spread of tumors to the liver from other areas, represents a deadly disease with poor prognosis. Currently, there is no effective therapeutic strategies and/or agents to combat ... Full text Cite

Lactate Is a Natural Suppressor of RLR Signaling by Targeting MAVS.

Journal Article Cell · June 27, 2019 RLR-mediated type I IFN production plays a pivotal role in elevating host immunity for viral clearance and cancer immune surveillance. Here, we report that glycolysis, which is inactivated during RLR activation, serves as a barrier to impede type I IFN pro ... Full text Open Access Link to item Cite

SETDB1-mediated methylation of Akt promotes its K63-linked ubiquitination and activation leading to tumorigenesis.

Journal Article Nat Cell Biol · February 2019 The serine/threonine kinase Akt plays a central role in cell proliferation, survival and metabolism, and its hyperactivation is linked to cancer progression. Here we report that Akt undergoes K64 methylation by SETDB1, which is crucial for cell membrane re ... Full text Link to item Cite

The critical role of AMPK in driving Akt activation under stress, tumorigenesis and drug resistance

Journal Article Nature Communications · November 9, 2018 AbstractPI3K/Akt signaling is activated in cancers and governs tumor initiation and progression, but how Akt is activated under diverse stresses is poorly understood. Here we identify AMPK as an essential regulator for Akt ... Full text Cite

Abnormal gametogenesis induced by p53 deficiency promotes tumor progression and drug resistance

Journal Article Cell Discovery · October 2, 2018 AbstractThe century-old embryonal/gametogenesis hypothesis of tumors could link diverse tumors’ malignant features together likely representing the real “stemness” of tumors. However, the genetic evidence to validate abnorm ... Full text Cite

Protocol to analyze the role of various metabolites in impacting global RNA 5-methylcytosine levels in cultured cells by dot blot.

Journal Article STAR Protoc · March 15, 2024 RNA 5-methylcytosine (m5C) modification critically impacts many biological processes. Here, we provide a protocol to analyze the role of various metabolites in impacting global RNA m5C levels in cultured cells by dot blot. We describe steps for treating cu ... Full text Link to item Cite

NSUN2 is a glucose sensor suppressing cGAS/STING to maintain tumorigenesis and immunotherapy resistance.

Journal Article Cell Metab · October 3, 2023 Glucose metabolism is known to orchestrate oncogenesis. Whether glucose serves as a signaling molecule directly regulating oncoprotein activity for tumorigenesis remains elusive. Here, we report that glucose is a cofactor binding to methyltransferase NSUN2 ... Full text Link to item Cite

Pyruvate dehydrogenase kinase supports macrophage NLRP3 inflammasome activation during acute inflammation.

Journal Article Cell Rep · January 31, 2023 Activating the macrophage NLRP3 inflammasome can promote excessive inflammation with severe cell and tissue damage and organ dysfunction. Here, we show that pharmacological or genetic inhibition of pyruvate dehydrogenase kinase (PDHK) significantly attenua ... Full text Open Access Link to item Cite

AMPK signaling and its targeting in cancer progression and treatment.

Journal Article Semin Cancer Biol · October 2022 The intrinsic mechanisms sensing the imbalance of energy in cells are pivotal for cell survival under various environmental insults. AMP-activated protein kinase (AMPK) serves as a central guardian maintaining energy homeostasis by orchestrating diverse ce ... Full text Link to item Cite

Identification of myo-inositol-binding proteins by using the biotin pull-down strategy in cultured cells.

Journal Article STAR Protoc · June 17, 2022 Metabolites are not only substrates in metabolic reactions, but they also serve as signaling molecules to regulate diverse biological functions. Identification of the binding proteins for the metabolites helps in the understanding of their functions beyond ... Full text Open Access Link to item Cite

The foundational framework of tumors: Gametogenesis, p53, and cancer

Journal Article Seminars in Cancer Biology · June 2022 Full text Cite

SIRPγ-expressing cancer stem-like cells promote immune escape of lung cancer via Hippo signaling.

Journal Article J Clin Invest · March 1, 2022 Cancer stem-like cells (CSLCs) acquire enhanced immune checkpoint responses to evade immune cell killing and promote tumor progression. Here we showed that signal regulatory protein γ (SIRPγ) determined CSLC properties and immune evasiveness in a small pop ... Full text Open Access Link to item Cite

Inositol serves as a natural inhibitor of mitochondrial fission by directly targeting AMPK.

Journal Article Mol Cell · September 16, 2021 Mitochondrial dynamics regulated by mitochondrial fusion and fission maintain mitochondrial functions, whose alterations underline various human diseases. Here, we show that inositol is a critical metabolite directly restricting AMPK-dependent mitochondria ... Full text Open Access Link to item Cite

Author Correction: SETDB1-mediated methylation of Akt promotes its K63-linked ubiquitination and activation leading to tumorigenesis.

Journal Article Nat Cell Biol · June 2021 A Correction to this paper has been published: https://doi.org/10.1038/s41556-021-00686-x. ... Full text Link to item Cite

AMPK maintains TCA cycle through sequential phosphorylation of PDHA to promote tumor metastasis

Journal Article Cell Stress · December 14, 2020 Cancer represents the leading public health problem throughout the world. Globally, about one out of six deaths is related to cancer, which is largely due to the metastatic lesions. However, there are no effective strategies for targeting cancer me ... Full text Cite

The Skp2 Pathway: A Critical Target for Cancer Therapy.

Journal Article Semin Cancer Biol · December 2020 Strictly regulated protein degradation by ubiquitin-proteasome system (UPS) is essential for various cellular processes whose dysregulation is linked to serious diseases including cancer. Skp2, a well characterized component of Skp2-SCF E3 ligase complex, ... Full text Open Access Link to item Cite

Phosphorylation of PDHA by AMPK Drives TCA Cycle to Promote Cancer Metastasis.

Journal Article Mol Cell · October 15, 2020 Cancer metastasis accounts for the major cause of cancer-related deaths. How disseminated cancer cells cope with hostile microenvironments in secondary site for full-blown metastasis is largely unknown. Here, we show that AMPK (AMP-activated protein kinase ... Full text Link to item Cite

Identification of primordial germ cell-like cells as liver metastasis initiating cells in mouse tumour models

Journal Article Cell Discovery · March 24, 2020 AbstractLiver metastasis, characterized by the spread of tumors to the liver from other areas, represents a deadly disease with poor prognosis. Currently, there is no effective therapeutic strategies and/or agents to combat ... Full text Cite

Lactate Is a Natural Suppressor of RLR Signaling by Targeting MAVS.

Journal Article Cell · June 27, 2019 RLR-mediated type I IFN production plays a pivotal role in elevating host immunity for viral clearance and cancer immune surveillance. Here, we report that glycolysis, which is inactivated during RLR activation, serves as a barrier to impede type I IFN pro ... Full text Open Access Link to item Cite

SETDB1-mediated methylation of Akt promotes its K63-linked ubiquitination and activation leading to tumorigenesis.

Journal Article Nat Cell Biol · February 2019 The serine/threonine kinase Akt plays a central role in cell proliferation, survival and metabolism, and its hyperactivation is linked to cancer progression. Here we report that Akt undergoes K64 methylation by SETDB1, which is crucial for cell membrane re ... Full text Link to item Cite

The critical role of AMPK in driving Akt activation under stress, tumorigenesis and drug resistance

Journal Article Nature Communications · November 9, 2018 AbstractPI3K/Akt signaling is activated in cancers and governs tumor initiation and progression, but how Akt is activated under diverse stresses is poorly understood. Here we identify AMPK as an essential regulator for Akt ... Full text Cite

Abnormal gametogenesis induced by p53 deficiency promotes tumor progression and drug resistance

Journal Article Cell Discovery · October 2, 2018 AbstractThe century-old embryonal/gametogenesis hypothesis of tumors could link diverse tumors’ malignant features together likely representing the real “stemness” of tumors. However, the genetic evidence to validate abnorm ... Full text Cite

H3 ubiquitination by NEDD4 regulates H3 acetylation and tumorigenesis

Journal Article Nature Communications · March 16, 2017 AbstractDynamic changes in histone modifications under various physiological cues play important roles in gene transcription and cancer. Identification of new histone marks critical for cancer development is of particular i ... Full text Cite

EGFR phosphorylation of DCBLD2 recruits TRAF6 and stimulates AKT-promoted tumorigenesis.

Journal Article J Clin Invest · September 2014 Aberrant activation of EGFR in human cancers promotes tumorigenesis through stimulation of AKT signaling. Here, we determined that the discoidina neuropilin-like membrane protein DCBLD2 is upregulated in clinical specimens of glioblastomas and head and nec ... Full text Open Access Link to item Cite

Akt: a new activation mechanism

Journal Article Cell Research · July 2014 Full text Cite

Toll-like receptor-mediated IRE1α activation as a therapeutic target for inflammatory arthritis.

Journal Article EMBO J · September 11, 2013 In rheumatoid arthritis (RA), macrophage is one of the major sources of inflammatory mediators. Macrophages produce inflammatory cytokines through toll-like receptor (TLR)-mediated signalling during RA. Herein, we studied macrophages from the synovial flui ... Full text Link to item Cite

Cycles of Ubiquitination and Deubiquitination Critically Regulate Growth Factor–Mediated Activation of Akt Signaling

Journal Article Science Signaling · January 8, 2013 The deubiquitinase CYLD suppresses activation of the tumor growth–promoting kinase Akt. ... Full text Cite

The role of Skp2 in hematopoietic stem cell quiescence, pool size, and self-renewal

Journal Article Blood · November 17, 2011 AbstractAlthough the maintenance of HSC quiescence and self-renewal are critical for controlling stem cell pool and transplantation efficiency, the mechanisms by which they are regulated remain largely unkno ... Full text Cite

PML Regulates Apoptosis at Endoplasmic Reticulum by Modulating Calcium Release

Journal Article Science · November 26, 2010 Promoting Apoptosis During acute disease, the promyelocytic leukemia (PML) protein becomes fused to another protein as a result of a chromosomal translocation. This protein appears to have multiple an ... Full text Cite

The E3 Ligase TRAF6 Regulates Akt Ubiquitination and Activation

Journal Article Science · August 28, 2009 Regulating Akt The protein kinase Akt is activated in response to receptor-activated generation of the signaling second messenger phosphatidylinositol 3,4,5-trisphosphate and has roles in regulation o ... Full text Cite

Cytoplasmic PML function in TGF-β signalling

Journal Article Nature · September 2004 Full text Cite