The HIF/PHF8/AR axis promotes prostate cancer progression.

Authors

D Tong
Q Liu
G Liu
W Yuan
L Wang
Y Guo
W Lan
Dianzheng Zhang, Philadelphia College of Osteopathic MedicineFollow
S Dong
Y Wang
H Xiao
J Mu
C Mao
J Wong
J Jiang

Document Type

Article

Publication Date

12-19-2016

Abstract

Recent studies provide strong evidence that the androgen receptor (AR) signaling pathway remains active in castration-resistant prostate cancer (CRPC). However, the underlying mechanisms are not well understood. In this study, we demonstrate that plant homeo domain finger protein 8 (PHF8 )interacts with and functions as an essential histone demethylase activity-dependent AR coactivator. Furthermore, we demonstrate that the expression of PHF8 is induced by hypoxia in various prostate cancer cell lines. Knockdown of either hypoxia-inducible factor HIF2α or HIF1α almost completely abolished hypoxia-induced PHF8 expression. Importantly, we observed that PHF8 is highly expressed in clinical androgen deprived prostate cancer samples and expression of PHF8 correlates with increased levels of HIF1α and HIF2α. Moreover, elevated PHF8 is associated with higher grade prostate cancers and unfavorable outcomes. Our findings support a working model in which hypoxia in castrated prostate cancer activates HIF transcription factors which then induces PHF8 expression. The elevated PHF8 in turn promotes the AR signaling pathway and prostate cancer progression. Therefore, the HIF/PHF8/AR axis could serve as a potential biomarker for CRPC and is also a promising therapeutic target in combating CRPC.

Publication Title

Oncogenesis

Volume

5

Issue

12

First Page

e283

Last Page

e295

PubMed ID

27991916

Comments

This article was published in Oncogenesis, Volume 5, Issue 12, Pages e283-e295 .

The published version is available at http://dx.doi.org/10.1038/oncsis.2016.74.

Copyright © 2016. Oncogenesis is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Recommended Citation

Tong, D; Liu, Q; Liu, G; Yuan, W; Wang, L; Guo, Y; Lan, W; Zhang, Dianzheng; Dong, S; Wang, Y; Xiao, H; Mu, J; Mao, C; Wong, J; and Jiang, J, "The HIF/PHF8/AR axis promotes prostate cancer progression." (2016). PCOM Scholarly Works. 1762.
https://digitalcommons.pcom.edu/scholarly_papers/1762