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Coregulators determine androgen receptor activity in prostate cancer
Kerim Yavuz1, Nathan A Lack1,2,3
1Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
Bioscience Reports
|August 20, 2025
Summary
Androgen receptor (AR) binding in prostate cancer (PCa) changes during disease progression, driven by coregulator proteins. These interactions influence AR
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- The androgen receptor (AR) drives most prostate cancer (PCa) by binding to DNA and altering gene expression.
- AR binding sites (cistrome) dynamically change during PCa initiation and progression, influencing disease growth and treatment resistance.
- These cistrome changes are increasingly linked to interactions with AR coregulator proteins, not just chromatin accessibility.
Purpose of the Study:
- To offer a novel perspective on the function of AR coregulators in AR transcriptional activity.
- To examine how AR coregulator interactions evolve throughout different stages of prostate cancer.
- To explore the therapeutic potential of targeting AR coregulators in advanced prostate cancer.
Main Methods:
- This review synthesizes emerging evidence on AR coregulator functions.
- It analyzes how coregulator interactions modulate AR DNA binding and gene activation.
- The review discusses the dynamic nature of the AR cistrome in PCa progression.
Main Results:
- AR coregulators stabilize AR binding to DNA, including low- to moderate-affinity sites.
- Coregulator interactions mediate locus-specific epigenetic modifications that promote transcription.
- Alterations in coregulator proteins are critical in defining normal versus oncogenic AR cistromes and AR-mediated transcription.
Conclusions:
- AR coregulators are pivotal in regulating AR transcriptional programs in prostate cancer.
- Understanding these dynamic coregulator interactions is key to deciphering PCa progression and therapeutic resistance.
- AR coregulators represent promising therapeutic targets for advanced prostate cancer.
Keywords:
androgen receptorcoregulator proteinsepigeneticsgene expression and regulationprostate cancerMore Related Videos
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