A Comprehensive Analysis of Coregulator Recruitment, Androgen Receptor Function and Gene Expression in Prostate Cancer

Overview

Journal Elife

Specialty Biology

Date 2017 Aug 23

PMID 28826481

Citations 41

Authors

Song Liu

Sangeeta Kumari

Qiang Hu

Dhirodatta Senapati

Varadha Balaji Venkadakrishnan

Dan Wang

Adam D DePriest

Simon E Schlanger

Salma Ben-Salem

Malyn May Valenzuela

Belinda Willard

Shaila Mudambi

Wendy M Swetzig

Gokul M Das

Mojgan Shourideh

Shahriah Koochekpour

Sara Moscovita Falzarano

Cristina Magi-Galluzzi

Neelu Yadav

Xiwei Chen

Changshi Lao

Jianmin Wang

Jean-Noel Billaud

Hannelore V Heemers

Affiliations

Soon will be listed here.

Abstract

Standard treatment for metastatic prostate cancer (CaP) prevents ligand-activation of androgen receptor (AR). Despite initial remission, CaP progresses while relying on AR. AR transcriptional output controls CaP behavior and is an alternative therapeutic target, but its molecular regulation is poorly understood. Here, we show that action of activated AR partitions into fractions that are controlled preferentially by different coregulators. In a 452-AR-target gene panel, each of 18 clinically relevant coregulators mediates androgen-responsiveness of 0-57% genes and acts as a coactivator or corepressor in a gene-specific manner. Selectivity in coregulator-dependent AR action is reflected in differential AR binding site composition and involvement with CaP biology and progression. Isolation of a novel transcriptional mechanism in which WDR77 unites the actions of AR and p53, the major genomic drivers of lethal CaP, to control cell cycle progression provides proof-of-principle for treatment via selective interference with AR action by exploiting AR dependence on coregulators.

Citing Articles

Reduction of Prostate Cancer Risk: Role of Frequent Ejaculation-Associated Mechanisms.

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The Homeobox Transcription Factor NKX3.1 Displays an Oncogenic Role in Castration-Resistant Prostate Cancer Cells.

Budreika A, Phoenix J, Kostlan R, Deegan C, Ferrari M, Young K Cancers (Basel). 2025; 17(2.

PMID: 39858088 PMC: 11763476. DOI: 10.3390/cancers17020306.

Context-specific targeting of the androgen receptor in prostate cancer.

Abate-Shen C Nat Genet. 2024; 56(10):2000-2001.

PMID: 39333765 DOI: 10.1038/s41588-024-01935-z.

Transcription Factors in Prostate Cancer: Insights for Disease Development and Diagnostic and Therapeutic Approaches.

Silva K, Tambwe N, Mahfouz D, Wium M, Cacciatore S, Paccez J Genes (Basel). 2024; 15(4).

PMID: 38674385 PMC: 11050257. DOI: 10.3390/genes15040450.

Race-specific coregulatory and transcriptomic profiles associated with DNA methylation and androgen receptor in prostate cancer.

Ramakrishnan S, Cortes-Gomez E, Athans S, Attwood K, Rosario S, Kim S Genome Med. 2024; 16(1):52.

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