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Shaping Chromatin States in Prostate Cancer by Pioneer Transcription Factors.

Publication ,  Journal Article
Hankey, W; Chen, Z; Wang, Q
Published in: Cancer Res
June 15, 2020

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.

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Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

June 15, 2020

Volume

80

Issue

12

Start / End Page

2427 / 2436

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Signal Transduction
  • Receptors, Androgen
  • Prostatic Neoplasms, Castration-Resistant
  • Prostate
  • Oncology & Carcinogenesis
  • Male
  • Humans
  • Homeodomain Proteins
  • Hepatocyte Nuclear Factor 3-alpha
 

Citation

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Hankey, W., Chen, Z., & Wang, Q. (2020). Shaping Chromatin States in Prostate Cancer by Pioneer Transcription Factors. Cancer Res, 80(12), 2427–2436. https://doi.org/10.1158/0008-5472.CAN-19-3447
Hankey, William, Zhong Chen, and Qianben Wang. “Shaping Chromatin States in Prostate Cancer by Pioneer Transcription Factors.Cancer Res 80, no. 12 (June 15, 2020): 2427–36. https://doi.org/10.1158/0008-5472.CAN-19-3447.
Hankey W, Chen Z, Wang Q. Shaping Chromatin States in Prostate Cancer by Pioneer Transcription Factors. Cancer Res. 2020 Jun 15;80(12):2427–36.
Hankey, William, et al. “Shaping Chromatin States in Prostate Cancer by Pioneer Transcription Factors.Cancer Res, vol. 80, no. 12, June 2020, pp. 2427–36. Pubmed, doi:10.1158/0008-5472.CAN-19-3447.
Hankey W, Chen Z, Wang Q. Shaping Chromatin States in Prostate Cancer by Pioneer Transcription Factors. Cancer Res. 2020 Jun 15;80(12):2427–2436.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

June 15, 2020

Volume

80

Issue

12

Start / End Page

2427 / 2436

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Signal Transduction
  • Receptors, Androgen
  • Prostatic Neoplasms, Castration-Resistant
  • Prostate
  • Oncology & Carcinogenesis
  • Male
  • Humans
  • Homeodomain Proteins
  • Hepatocyte Nuclear Factor 3-alpha