@article{fc7e8a50c5a846e99755ceca48b0e0a4,
title = "BMI1 regulates androgen receptor in prostate cancer independently of the polycomb repressive complex 1",
abstract = "BMI1, a polycomb group (PcG) protein, plays a critical role in epigenetic regulation of cell differentiation and proliferation, and cancer stem cell self-renewal. BMI1 is upregulated in multiple types of cancer, including prostate cancer. As a key component of polycomb repressive complex 1 (PRC1), BMI1 exerts its oncogenic functions by enhancing the enzymatic activities of RING1B to ubiquitinate histone H2A at lysine 119 and repress gene transcription. Here, we report a PRC1-independent role of BMI1 that is critical for castration-resistant prostate cancer (CRPC) progression. BMI1 binds the androgen receptor (AR) and prevents MDM2-mediated AR protein degradation, resulting in sustained AR signaling in prostate cancer cells. More importantly, we demonstrate that targeting BMI1 effectively inhibits tumor growth of xenografts that have developed resistance to surgical castration and enzalutamide treatment. These results suggest that blocking BMI1 alone or in combination with anti-AR therapy can be more efficient to suppress prostate tumor growth.",
author = "Sen Zhu and Dongyu Zhao and Lin Yan and Weihua Jiang and Kim, {Jung Sun} and Bingnan Gu and Qipeng Liu and Rui Wang and Bo Xia and Zhao, {Jonathan C.} and Gang Song and Wenyi Mi and Wang, {Rong Fu} and Xiaobing Shi and Lam, {Hung Ming} and Xuesen Dong and Jindan Yu and Kaifu Chen and Qi Cao",
note = "Funding Information: We appreciate Arul M. Chinnaiyan{\textquoteright}s strong support for this work. We thank Haojie Huang for AR-V7 and AR-Ve567s plasmids, Arul M. Chinnaiyan and Xiaoju Wang for Halo-AR, Halo-AR-NTD, Halo-AR-DBD, Halo-AR-LBD, GST-BMI1, and GST-RING1B plasmids, and Eva Corey for the LuCaP 35CR and LuCaP 86.2CR patient-derived xenografts (PDX). We thank The University of Texas MD Anderson Cancer Center Science Park Next-Generation Sequencing (NGS) Facility (supported by CPRIT grants RP120348 and RP170002) for assistance with next-generation sequencing, and the Houston Methodist Comparative Medicine core facility, Jenny Chang, Anthony Kozielski, and Wei Qian for assistance with in vivo work. We thank Johnique Atkins for comments and editing this manuscript. This work is supported in part by grants from Houston Methodist Research Institute, Prostate Cancer Foundation (13YOUN007 to Q.C.), U.S. Department of Defense (W81XWH-15-1-0639 and W81XWH-17-1-0357 to Q.C.), American Cancer Society (TBE-128382 to Q.C.), and NIH/NCI (R01CA208257 to Q.C.); K.C. is supported in part by grants from NIH/NHLBI (R01CA208257, HL100397, and HL099997) and Department of Defense (W81XWH-17-1-0357); R.-F.W. is supported by grants from the NCI, NIH (R01CA101795 and U54CA210181), Department of Defense (W81XWH-16-1-0417), and Cancer Prevention and Research Institute of Texas (CPRIT; DP150099, RP150611, and RP170537). X.D. is supported by Canadian Institute of Health Research (#MOP-137007). H.-M.L. is a recipient of the Young Investigator Award from the Prostate Cancer Foundation, an Idea Development Award from the Department of Defense (W81XWH-14-1-0271), and a FHCRC/UW Cancer Consortium New Investigator Grant of NIH P30 CA015704. J.Y. is supported by NIH/NCI (R01CA172384), Department of Defense (W81XWH-17-1-0405, W81XWH-17-1-0362, and W81XWH-17-1-0578). X.S. is supported by grants from NIH/NCI (1R01CA204020-01). X.S. is a Leukemia & Lymphoma Society Career Development Program scholar. W.M. is an MD Anderson Center for Cancer Epigenetics postdoctoral scholar. J.C.Z. is supported by grants from NIH/NCI (1R50CA211271-01). Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = feb,
day = "5",
doi = "10.1038/s41467-018-02863-3",
language = "English (US)",
volume = "9",
journal = "Nat Commun",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}