Shaping Chromatin States in Prostate Cancer by Pioneer Transcription Factors.

Journal Article (Journal Article;Review)

The androgen receptor (AR) is a critical therapeutic target in prostate cancer that responds to antagonists in primary disease, but inevitably becomes reactivated, signaling onset of the lethal castration-resistant prostate cancer (CRPC) stage. Epigenomic investigation of the chromatin environment and interacting partners required for AR transcriptional activity has uncovered three pioneer factors that open up chromatin and facilitate AR-driven transcriptional programs. FOXA1, HOXB13, and GATA2 are required for normal AR transcription in prostate epithelial development and for oncogenic AR transcription during prostate carcinogenesis. AR signaling is dependent upon these three pioneer factors both before and after the clinical transition from treatable androgen-dependent disease to untreatable CRPC. Agents targeting their respective DNA binding or downstream chromatin-remodeling events have shown promise in preclinical studies of CRPC. AR-independent functions of FOXA1, HOXB13, and GATA2 are emerging as well. While all three pioneer factors exert effects that promote carcinogenesis, some of their functions may inhibit certain stages of prostate cancer progression. In all, these pioneer factors represent some of the most promising potential therapeutic targets to emerge thus far from the study of the prostate cancer epigenome.

Full Text

Duke Authors

Cited Authors

  • Hankey, W; Chen, Z; Wang, Q

Published Date

  • June 15, 2020

Published In

Volume / Issue

  • 80 / 12

Start / End Page

  • 2427 - 2436

PubMed ID

  • 32094298

Pubmed Central ID

  • 32094298

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-19-3447

Language

  • eng

Conference Location

  • United States