Abstract 7247: BPTF regulates androgen receptor activity in prostate cancer

Abstract BPTF, the scaffolding subunit of the nucleosome remodeling factor (NURF) complex, has been implicated in the progression of several malignancies, but its role in prostate cancer (PCa) remains unclear. Here, we show that BPTF is upregulated in aggressive PCa and promotes disease progression. BPTF knockdown inhibits PCa cell proliferation, while CRISPRa-mediated upregulation promotes androgen-independent growth. To investigate BPTF function, we performed RNA-seq, ChIP-seq and ATAC-seq analyses in BPTF-knockdown PCa cells. RNA-seq analysis reveals that BPTF primarily upregulates androgen receptor (AR) target gene expression. ChIP-seq data show that BPTF facilitates AR binding to enhancers, super-enhancers as well as promoters. ATAC-seq data indicates that BPTF enhances chromatin accessibility at AR-binding sites, partly via SMARCA1, a catalytic subunit of the NURF complex. Notably, BPTF ChIP-seq peaks exhibit strong enrichment of FOXA1 motifs but weak enrichment of AR motifs. We find that BPTF interacts with both FOXA1 and AR to form a protein complex in which FOXA1 anchors BPTF-AR to chromatin, while BPTF stabilizes the AR-FOXA1 interaction. Importantly, BPTF interacts with AR through its bromodomain, and a bromodomain inhibitor disrupts this interaction, leading to impaired AR signaling and suppressed PCa cell growth. In summary, our findings establish BPTF as a key regulator of AR activity by enhancing chromatin accessibility and stabilizing the AR-FOXA1 complex, highlighting BPTF as a potential therapeutic target for prostate cancer. Citation Format: Hee-Young Jeon, Sudeep Khadka, Majid Pornour, Hyunju Ryu, Hegang Chen, Arif Hussain, Hung-Ming Lam, Eva Corey, Htoo Zarni Oo, Martin E. Gleave, Xiaofang Che, Christopher E. Barbieri, Jianfei Qi. BPTF regulates androgen receptor activity in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7247.