Diverse AR-V7 cistromes in castration-resistant prostate cancer are governed by HoxB13
Abstract
Mechanisms underlying androgen receptor (AR) splice variant 7 (AR-V7) oncogenic function at the genomic level remain poorly defined. Studies here found that AR-V7 cistromes are cell-context–dependent in castration-resistant prostate cancer (CRPC) cells and tissues, resulting in tremendous diversity in AR-V7–regulated transcriptomes across CRPC patients. Thus, few downstream targets of AR-V7 can universally account for CRPC progression, leaving us without adequate, common, viable therapeutic targets for this heterogeneous disease in which AR-V7 itself is not druggable by antiandrogens. Remarkably, we discovered that HoxB13 governs the diverse AR-V7 cistromes among CRPC, thus shifting focus from the previously characterized role of HoxB13 in androgen-dependent prostate cancer to a distinct role in CRPC. These findings will significantly impact therapeutic strategies for AR-V7–driven CRPC, for which there is no approved therapy.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 29, 2018
- Source ID
- 10.1073/pnas.1718811115
Entities
People
- Benjamin Sunkel
- Changxue Lu
- Connor Geraghty
- Dayong Wu
- Emmanuel S. Antonarakis
- Jennifer M. Thomas-ahner
- Jiaoti Huang
- Jun Luo
- Pearlly S. Yan
- Pei Zhao
- Qi-En Wang
- Qianben Wang
- Qingfu Zhang
- Steven K. Clinton
- Tim H-M Huang
- Victor X. Jin
- William Hankey
- Xiaolong Cheng
- Zhihua Liu
- Zhong Chen
Organizations
- Duke University
- Johns Hopkins University
- National Institutes of Health
- Ohio State University
- Peking Union Medical College
- Prostate Cancer Foundation
- St. Jude Children's Research Hospital
- United States Department of Defense
- University of Texas Health Science Center at San Antonio