Abstract LB-207: A novel role for polycomb group protein BMI1 in prostate cancer

Abstract

Abstract BMI1, a Polycomb Group (PcG) protein, plays a critical role in epigenetic regulation of cancer stem cell self-renewal, cell differentiation and proliferation. BMI1 is upregulated in multiple types of cancer, including prostate cancer. As a key component of Polycomb Repressive Complex 1 (PRC1), BMI1 can exert 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 castrate-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. Citation Format: Sen Zhu, Dongyu Zhang, Lin Yan, Weihua Jiang, Qipeng Liu, Rui Wang, Bo Xia, Jonathan C. Zhao, Rong-Fu Wang, Xiaobing Shi, Hung-ming Lam, Xuesen Dong, Jindan Yu, Kaifu Chen, Qi Cao. A novel role for polycomb group protein BMI1 in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-207.