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Everardo Macias

Assistant Professor in Pathology
Pathology
DUMC 2626, 571 Research Drive MSRB-1, Durham, NC 27710
905 S. La Salle St., GSRB1 Room 2079, Durham, NC 27710

Selected Publications


Targeting glutamine dependence with DRP-104 inhibits proliferation and tumor growth of castration-resistant prostate cancer.

Journal Article Prostate · March 2024 BACKGROUND: Prostate cancer (PCa) continues to be one of the leading causes of cancer deaths in men. While androgen deprivation therapy is initially effective, castration-resistant PCa (CRPC) often recurs and has limited treatment options. Our previous stu ... Full text Link to item Cite

Heat shock factor 1 directly regulates transsulfuration pathway to promote prostate cancer proliferation and survival.

Journal Article Commun Biol · January 3, 2024 There are limited therapeutic options for patients with advanced prostate cancer (PCa). We previously found that heat shock factor 1 (HSF1) expression is increased in PCa and is an actionable target. In this manuscript, we identify that HSF1 regulates the ... Full text Open Access Link to item Cite

The effects of glycemic index on prostate cancer progression in a xenograft mouse model.

Journal Article Prostate Cancer Prostatic Dis · December 11, 2023 BACKGROUND: Previously, we found low-carbohydrate diets slowed prostate cancer (PC) growth and increased survival vs. a Western diet in mice, by inhibiting the insulin/IGF-1 axis. Thus, we tested whether modifying carbohydrate quality to lower glycemic ind ... Full text Link to item Cite

Targeting the Divergent Roles of STK3 Inhibits Breast Cancer Cell Growth and Opposes Doxorubicin-Induced Cardiotoxicity In Vitro.

Journal Article Cancers (Basel) · May 18, 2023 Breast cancer (BCa) is the most prevalent type of cancer in women. Several therapies used in the treatment of breast cancer are associated with clinically important rates of cardiovascular toxicity during or after treatment exposure, including anthracyclin ... Full text Link to item Cite

Cyclin-dependent kinase 4 expression alters the number of keratinocyte stem cells in the mouse hair follicle.

Journal Article Cell Biol Int · May 2022 Hair follicles regenerate periodically by spontaneously undergoing cycles of growth, regression, and relative quiescence. During the hair cycle, follicle stem cells residing in a specialized niche remain quiescent, and they are stimulated to proliferate th ... Full text Link to item Cite

NUAK family kinase 2 is a novel therapeutic target for prostate cancer.

Journal Article Mol Carcinog · March 2022 Current advancements in prostate cancer (PC) therapies have been successful in slowing PC progression and increasing life expectancy; however, there is still no curative treatment for advanced metastatic castration resistant PC (mCRPC). Most treatment opti ... Full text Link to item Cite

MESH1 knockdown triggers proliferation arrest through TAZ repression.

Journal Article Cell death & disease · March 2022 All organisms are constantly exposed to various stresses, necessitating adaptive strategies for survival. In bacteria, the main stress-coping mechanism is the stringent response triggered by the accumulation of "alarmone" (p)ppGpp to arrest proliferation a ... Full text Cite

Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer.

Journal Article Mol Ther · January 5, 2022 Serine/threonine kinase 3 (STK3) is an essential member of the highly conserved Hippo tumor suppressor pathway that regulates Yes-associated protein 1 (YAP1) and TAZ. STK3 and its paralog STK4 initiate a phosphorylation cascade that regulates YAP1/TAZ inhi ... Full text Link to item Cite

27-Hydroxycholesterol Impairs Plasma Membrane Lipid Raft Signaling as Evidenced by Inhibition of IL6-JAK-STAT3 Signaling in Prostate Cancer Cells.

Journal Article Mol Cancer Res · May 2020 We recently reported that restoring the CYP27A1-27hydroxycholesterol axis had antitumor properties. Thus, we sought to determine the mechanism by which 27HC exerts its anti-prostate cancer effects. As cholesterol is a major component of membrane microdomai ... Full text Link to item Cite

NUAK2 inhibition for prostate cancer.

Conference MOLECULAR CANCER RESEARCH · 2020 Cite

Abstract 3590: Mechanisms and inhibition RIOK2 for obesity-driven prostate cancer

Conference Cancer Research · July 1, 2019 AbstractObesity is associated with greater risk of high-grade prostate cancer (PC), recurrence after therapy, metastases, and PC specific mortality. The fact that obesity is a PC risk factor creates an oppor ... Full text Cite

Abstract 862: Inhibition of Hippo tumor suppressors MST1/2 slows prostate cancer cell proliferation and invasion

Conference Cancer Research · July 1, 2019 AbstractSerine/threonine kinase 3 (STK3) and its paralog STK4, encode MST2 and MST1 kinases respectively, which are essential members of the highly conserved Hippo Tumor suppressor pathway which regulate Yes ... Full text Cite

A Low Glycemic Index Diet Slows Prostate Cancer Growth (P05-018-19).

Journal Article Curr Dev Nutr · June 2019 Objectives: Carbohydrates are the main source of energy in older adults in the US. Moreover, they increase insulin and insulin-like growth factor-1 (IGF1), which are implicated in tumor growth by increasing cell survival. Previously, we found low carbohydr ... Full text Link to item Cite

Serum cholesterol levels and tumor growth in a PTEN-null transgenic mouse model of prostate cancer.

Journal Article Prostate Cancer Prostatic Dis · June 2018 BACKGROUND: Some, but not all, epidemiologic evidence supports a role for cholesterol, the precursor for steroid hormone synthesis, in prostate cancer. Using a PTEN-null transgenic mouse model of prostate cancer, we tested the effect of modifying serum cho ... Full text Link to item Cite

Angiotensin receptor signaling and prostate tumor growth in mice.

Journal Article J Exp Ther Oncol · September 2017 The renin-angiotensin system, through its type 1 and type 2 angiotensin receptors (AT1R and AT2R, respectively) may have a role in prostate cancer. The objective of this pilot study was to explore that potential role by determining whether the AT1R blocker ... Link to item Cite

Impact of carbohydrate restriction in the context of obesity on prostate tumor growth in the Hi-Myc transgenic mouse model.

Journal Article Prostate Cancer Prostatic Dis · June 2017 BACKGROUND: Previously, we showed that carbohydrate restriction with calorie restriction slowed tumor growth in xenograft mouse prostate cancer models. Herein, we examined the impact of carbohydrate restriction without calorie restriction on tumor developm ... Full text Link to item Cite

Evidence for Feedback Regulation Following Cholesterol Lowering Therapy in a Prostate Cancer Xenograft Model.

Journal Article Prostate · April 2017 BACKGROUND: Epidemiologic data suggest cholesterol-lowering drugs may prevent the progression of prostate cancer, but not the incidence of the disease. However, the association of combination therapy in cholesterol reduction on prostate or any cancer is un ... Full text Link to item Cite

CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer.

Journal Article Cancer Res · April 1, 2017 In this study, we used a bioinformatic approach to identify genes whose expression is dysregulated in human prostate cancers. One of the most dramatically downregulated genes identified encodes CYP27A1, an enzyme involved in regulating cellular cholesterol ... Full text Link to item Cite

A novel mechanism of skin tumor promotion involving interferon-gamma (IFNγ)/signal transducer and activator of transcription-1 (Stat1) signaling.

Journal Article Mol Carcinog · August 2015 The current study was designed to explore the role of signal transducer and activator of transcription 1 (Stat1) during tumor promotion using the mouse skin multistage carcinogenesis model. Topical treatment with both 12-O-tetradecanoylphorbol-13-acetate ( ... Full text Link to item Cite

Targeting glutamine dependence with DRP-104 inhibits proliferation and tumor growth of castration-resistant prostate cancer.

Journal Article Prostate · March 2024 BACKGROUND: Prostate cancer (PCa) continues to be one of the leading causes of cancer deaths in men. While androgen deprivation therapy is initially effective, castration-resistant PCa (CRPC) often recurs and has limited treatment options. Our previous stu ... Full text Link to item Cite

Heat shock factor 1 directly regulates transsulfuration pathway to promote prostate cancer proliferation and survival.

Journal Article Commun Biol · January 3, 2024 There are limited therapeutic options for patients with advanced prostate cancer (PCa). We previously found that heat shock factor 1 (HSF1) expression is increased in PCa and is an actionable target. In this manuscript, we identify that HSF1 regulates the ... Full text Open Access Link to item Cite

The effects of glycemic index on prostate cancer progression in a xenograft mouse model.

Journal Article Prostate Cancer Prostatic Dis · December 11, 2023 BACKGROUND: Previously, we found low-carbohydrate diets slowed prostate cancer (PC) growth and increased survival vs. a Western diet in mice, by inhibiting the insulin/IGF-1 axis. Thus, we tested whether modifying carbohydrate quality to lower glycemic ind ... Full text Link to item Cite

Targeting the Divergent Roles of STK3 Inhibits Breast Cancer Cell Growth and Opposes Doxorubicin-Induced Cardiotoxicity In Vitro.

Journal Article Cancers (Basel) · May 18, 2023 Breast cancer (BCa) is the most prevalent type of cancer in women. Several therapies used in the treatment of breast cancer are associated with clinically important rates of cardiovascular toxicity during or after treatment exposure, including anthracyclin ... Full text Link to item Cite

Cyclin-dependent kinase 4 expression alters the number of keratinocyte stem cells in the mouse hair follicle.

Journal Article Cell Biol Int · May 2022 Hair follicles regenerate periodically by spontaneously undergoing cycles of growth, regression, and relative quiescence. During the hair cycle, follicle stem cells residing in a specialized niche remain quiescent, and they are stimulated to proliferate th ... Full text Link to item Cite

NUAK family kinase 2 is a novel therapeutic target for prostate cancer.

Journal Article Mol Carcinog · March 2022 Current advancements in prostate cancer (PC) therapies have been successful in slowing PC progression and increasing life expectancy; however, there is still no curative treatment for advanced metastatic castration resistant PC (mCRPC). Most treatment opti ... Full text Link to item Cite

MESH1 knockdown triggers proliferation arrest through TAZ repression.

Journal Article Cell death & disease · March 2022 All organisms are constantly exposed to various stresses, necessitating adaptive strategies for survival. In bacteria, the main stress-coping mechanism is the stringent response triggered by the accumulation of "alarmone" (p)ppGpp to arrest proliferation a ... Full text Cite

Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer.

Journal Article Mol Ther · January 5, 2022 Serine/threonine kinase 3 (STK3) is an essential member of the highly conserved Hippo tumor suppressor pathway that regulates Yes-associated protein 1 (YAP1) and TAZ. STK3 and its paralog STK4 initiate a phosphorylation cascade that regulates YAP1/TAZ inhi ... Full text Link to item Cite

27-Hydroxycholesterol Impairs Plasma Membrane Lipid Raft Signaling as Evidenced by Inhibition of IL6-JAK-STAT3 Signaling in Prostate Cancer Cells.

Journal Article Mol Cancer Res · May 2020 We recently reported that restoring the CYP27A1-27hydroxycholesterol axis had antitumor properties. Thus, we sought to determine the mechanism by which 27HC exerts its anti-prostate cancer effects. As cholesterol is a major component of membrane microdomai ... Full text Link to item Cite

NUAK2 inhibition for prostate cancer.

Conference MOLECULAR CANCER RESEARCH · 2020 Cite

Abstract 3590: Mechanisms and inhibition RIOK2 for obesity-driven prostate cancer

Conference Cancer Research · July 1, 2019 AbstractObesity is associated with greater risk of high-grade prostate cancer (PC), recurrence after therapy, metastases, and PC specific mortality. The fact that obesity is a PC risk factor creates an oppor ... Full text Cite

Abstract 862: Inhibition of Hippo tumor suppressors MST1/2 slows prostate cancer cell proliferation and invasion

Conference Cancer Research · July 1, 2019 AbstractSerine/threonine kinase 3 (STK3) and its paralog STK4, encode MST2 and MST1 kinases respectively, which are essential members of the highly conserved Hippo Tumor suppressor pathway which regulate Yes ... Full text Cite

A Low Glycemic Index Diet Slows Prostate Cancer Growth (P05-018-19).

Journal Article Curr Dev Nutr · June 2019 Objectives: Carbohydrates are the main source of energy in older adults in the US. Moreover, they increase insulin and insulin-like growth factor-1 (IGF1), which are implicated in tumor growth by increasing cell survival. Previously, we found low carbohydr ... Full text Link to item Cite

Serum cholesterol levels and tumor growth in a PTEN-null transgenic mouse model of prostate cancer.

Journal Article Prostate Cancer Prostatic Dis · June 2018 BACKGROUND: Some, but not all, epidemiologic evidence supports a role for cholesterol, the precursor for steroid hormone synthesis, in prostate cancer. Using a PTEN-null transgenic mouse model of prostate cancer, we tested the effect of modifying serum cho ... Full text Link to item Cite

Angiotensin receptor signaling and prostate tumor growth in mice.

Journal Article J Exp Ther Oncol · September 2017 The renin-angiotensin system, through its type 1 and type 2 angiotensin receptors (AT1R and AT2R, respectively) may have a role in prostate cancer. The objective of this pilot study was to explore that potential role by determining whether the AT1R blocker ... Link to item Cite

Impact of carbohydrate restriction in the context of obesity on prostate tumor growth in the Hi-Myc transgenic mouse model.

Journal Article Prostate Cancer Prostatic Dis · June 2017 BACKGROUND: Previously, we showed that carbohydrate restriction with calorie restriction slowed tumor growth in xenograft mouse prostate cancer models. Herein, we examined the impact of carbohydrate restriction without calorie restriction on tumor developm ... Full text Link to item Cite

Evidence for Feedback Regulation Following Cholesterol Lowering Therapy in a Prostate Cancer Xenograft Model.

Journal Article Prostate · April 2017 BACKGROUND: Epidemiologic data suggest cholesterol-lowering drugs may prevent the progression of prostate cancer, but not the incidence of the disease. However, the association of combination therapy in cholesterol reduction on prostate or any cancer is un ... Full text Link to item Cite

CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer.

Journal Article Cancer Res · April 1, 2017 In this study, we used a bioinformatic approach to identify genes whose expression is dysregulated in human prostate cancers. One of the most dramatically downregulated genes identified encodes CYP27A1, an enzyme involved in regulating cellular cholesterol ... Full text Link to item Cite

A novel mechanism of skin tumor promotion involving interferon-gamma (IFNγ)/signal transducer and activator of transcription-1 (Stat1) signaling.

Journal Article Mol Carcinog · August 2015 The current study was designed to explore the role of signal transducer and activator of transcription 1 (Stat1) during tumor promotion using the mouse skin multistage carcinogenesis model. Topical treatment with both 12-O-tetradecanoylphorbol-13-acetate ( ... Full text Link to item Cite

Constitutive Stat3 activation alters behavior of hair follicle stem and progenitor cell populations.

Journal Article Mol Carcinog · February 2015 STATs play crucial roles in a wide variety of biological functions, including development, proliferation, differentiation and migration as well as in cancer development. In the present study, we examined the impact of constitutive activation of Stat3 on be ... Full text Link to item Cite

Abstract 2970: Differential effects of caloric and carbohydrate restriction on prostate cancer in a mouse model

Conference Cancer Research · October 1, 2014 AbstractProstate cancer (PC) is the most common non-cutaneous malignancy in men in the United States. Animal studies have shown that dietary interventions, specifically dietary restriction, demonstrate an ab ... Full text Cite

Stat3 binds to mtDNA and regulates mitochondrial gene expression in keratinocytes.

Journal Article J Invest Dermatol · July 2014 The nuclear transcription factor signal transducer and activator of transcription 3 (Stat3) has recently been reported to have a localized mitochondrial regulatory function. Current data suggest that mitochondrial Stat3 (mitoStat3) is necessary for maximal ... Full text Link to item Cite

Skp2 deficiency inhibits chemical skin tumorigenesis independent of p27(Kip1) accumulation.

Journal Article Am J Pathol · May 2013 S-phase kinase-associated protein 2 (Skp2) functions as the receptor component of the Skp-Cullin-F-box complex and is implicated in the degradation of several cell cycle regulators, such as p21(Cip1), p27(Kip1), p57(Kip2), and cyclin E. Numerous studies in ... Full text Link to item Cite

Skp2 is necessary for Myc-induced keratinocyte proliferation but dispensable for Myc oncogenic activity in the oral epithelium

Journal Article American Journal of Pathology · January 1, 2011 The proto-oncogene c-Myc encodes a transcription factor that is implicated in the regulation of cellular proliferation, differentiation, and apoptosis. Myc accelerates the rate of cell proliferation, at least in part, through its ability to down-regulate t ... Full text Cite

An ARF-independent c-MYC-activated tumor suppression pathway mediated by ribosomal protein-Mdm2 Interaction.

Journal Article Cancer Cell · September 14, 2010 In vitro studies have shown that inhibition of ribosomal biogenesis can activate p53 through ribosomal protein (RP)-mediated suppression of Mdm2 E3 ligase activity. To study the physiological significance of the RP-Mdm2 interaction, we generated mice carry ... Full text Link to item Cite

Role of cyclin D1 as a mediator of c-Met- and beta-catenin-induced hepatocarcinogenesis.

Journal Article Cancer Res · January 1, 2009 Activation of c-Met signaling and beta-catenin mutations are frequent genetic events observed in liver cancer development. Recently, we demonstrated that activated beta-catenin can cooperate with c-Met to induce liver cancer formation in a mouse model. Cyc ... Full text Link to item Cite

CDK2 activation in mouse epidermis induces keratinocyte proliferation but does not affect skin tumor development.

Journal Article Am J Pathol · August 2008 It has been widely assumed that elevated CDK2 kinase activity plays a contributory role in tumorigenesis. We have previously shown that mice overexpressing CDK4 under control of the keratin 5 promoter (K5CDK4 mice) develop epidermal hyperplasia and increas ... Full text Link to item Cite

Expression of CDK4 or CDK2 in mouse oral cavity is retained in adult pituitary with distinct effects on tumorigenesis.

Journal Article Cancer Res · January 1, 2008 The keratin 5 (K5) promoter drives transgenic expression to the basal cell layer of stratified epithelia. Surprisingly, analysis of K5CDK4 and K5CDK2 transgenic mouse embryos showed CDK4 and CDK2 expression not only in the expected tissues, but also in the ... Full text Link to item Cite

Cdk2 deficiency decreases ras/CDK4-dependent malignant progression, but not myc-induced tumorigenesis.

Journal Article Cancer Res · October 15, 2007 We have previously shown that forced expression of CDK4 in mouse skin (K5CDK4 mice) results in increased susceptibility to squamous cell carcinoma (SCC) development in a chemical carcinogenesis protocol. This protocol induces skin papilloma development, ca ... Full text Link to item Cite

Genetic mosaics reveal both cell-autonomous and cell-nonautonomous function of murine p27Kip1.

Journal Article Proc Natl Acad Sci U S A · March 14, 2006 Loss of the cyclin-dependent kinase inhibitor p27(Kip1) leads to an overall increase in animal growth, pituitary tumors, and hyperplasia of hematopoietic organs, yet it is unknown whether all cells function autonomously in response to p27(Kip1) activity or ... Full text Link to item Cite

Lack of cyclin-dependent kinase 4 inhibits c-myc tumorigenic activities in epithelial tissues.

Journal Article Mol Cell Biol · September 2004 The proto-oncogene c-myc encodes a transcription factor that is implicated in the regulation of cellular proliferation, differentiation, and apoptosis and that has also been found to be deregulated in several forms of human and experimental tumors. We have ... Full text Link to item Cite

Enhanced malignant tumorigenesis in Cdk4 transgenic mice.

Journal Article Oncogene · March 11, 2004 In a previous study, we reported that overexpression of cyclin-dependent kinase-4 (CDK4) in mouse epidermis results in epidermal hyperplasia, hypertrophy and severe dermal fibrosis. In this study, we have investigated the susceptibility to skin tumor forma ... Full text Link to item Cite