Androgen deprivation–induced NCoA2 promotes metastatic and castration-resistant prostate cancer

Qin, Jun; Lee, Hui Ju; Wu, San‐Pin; Lin, Shih Chieh; Lanz, Rainer B.; Creighton, Chad J.; DeMayo, Francesco J.; Tsai, Sophia Y.; Tsai, Ming Jer

doi:10.1172/jci76412

Cited by 84 publications

(86 citation statements)

References 49 publications

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“…Analysis of human tumor data sets was carried out essentially as previously described (11,38,55). The Rac1 gene signature was derived from the gene expression profile of the colon cancer cell line SW480 (GSE78093).…”

Section: Methodsmentioning

confidence: 99%

“…The WHSC1 gene signature was derived from our own gene expression profile data set (GSE84868), which consisted of 960 upregulated and 1,270 downregulated unique human genes. To define the degree of gene signature manifestation within the profiles from an external human tumor data set (e.g., GSE21032), we used the previously described t score metric (11,(55)(56)(57). For example, the t score was defined for each external profile as the 2-sided t-statistic comparing the average of the WHSC1-induced genes with the average of the WHSC1-repressed genes (genes within the human tumor data set were first centered to SDs from the median of the primary tumor specimens).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

AKT-mediated stabilization of histone methyltransferase WHSC1 promotes prostate cancer metastasis

Ni¹,

Xue²,

Yuan³

et al. 2017

Journal of Clinical Investigation

Self Cite

102

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

AKT-mediated stabilization of histone methyltransferase WHSC1 promotes prostate cancer metastasis

Ni¹,

Xue²,

Yuan³

et al. 2017

Journal of Clinical Investigation

Self Cite

102

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“…Mechanistically, increased SRC expression enhances AR signaling in low androgen settings and also potentiates alternative ligand usage (Agoulnik & Weigel 2009, Foley & Mitsiades 2016. The clinical relevance of these factors is perhaps best emphasized by the finding that constitutive overexpression of SRC-2 in the mouse prostate epithelium was sufficient for the development of prostate adenocarcinoma in mice, whereas SRC-2 depletion prevented CRPC development in PTEN-deficient mice (Qin et al 2014).…”

Section: Ar Coregulator Alterations In Crpcmentioning

confidence: 99%

Androgen receptor signaling in castration-resistant prostate cancer: a lesson in persistence

Coutinho¹,

Day²,

Tilley³

et al. 2016

Endocrine-Related Cancer

137

113

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The androgen receptor (AR) signaling axis drives all stages of prostate cancer, including the lethal, drug-resistant form of the disease termed castration-resistant prostate cancer (CRPC), which arises after failure of androgen deprivation therapy (ADT). Persistent AR activity in spite of ADT and the second-generation AR-targeting agents enzalutamide and abiraterone is achieved in many cases by direct alterations to the AR signaling axis. Herein, we provide a detailed description of how such alterations contribute to the development and progression of CRPC. Aspects of this broad and ever-evolving field specifically addressed in this review include: the etiology and significance of increased AR expression; the frequency and role of gain-of-function mutations in the AR gene; the function of constitutively active, truncated forms of the AR termed AR variants and the clinical relevance of alterations to the activity and expression of AR coregulators. Additionally, we examine the novel therapeutic strategies to inhibit these classes of therapy resistance mechanisms, with an emphasis on emerging agents that act in a manner distinct from the current ligand-centric approaches. Throughout, we discuss how the central role of AR in prostate cancer and the constant evolution of the AR signaling axis during disease progression represent archetypes of two key concepts in oncology, oncogene addiction and therapy-mediated selection pressure.

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“…NCOA2 depletion reduces AR-dependent gene expression in PCa cells (74). Moreover, in a genetically engineered mouse model, overexpression of NCOA2 in the prostate epithelium drives neoplasia and promotes metastasis through hyperactivation of growth factor signaling (76). Therefore, NCOA2 contributes to endocrine therapy-resistant phenotypes by promoting AR-dependent and -independent mechanisms.…”

Section: Alterations In Collaborating Factorsmentioning

confidence: 99%

Role of steroid receptor and coregulator mutations in hormone-dependent cancers

Groner¹,

Brown²

2017

Journal of Clinical Investigation

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Androgen deprivation–induced NCoA2 promotes metastatic and castration-resistant prostate cancer

Cited by 84 publications

References 49 publications

AKT-mediated stabilization of histone methyltransferase WHSC1 promotes prostate cancer metastasis

AKT-mediated stabilization of histone methyltransferase WHSC1 promotes prostate cancer metastasis

Androgen receptor signaling in castration-resistant prostate cancer: a lesson in persistence

Role of steroid receptor and coregulator mutations in hormone-dependent cancers

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