| Literature DB >> 27238081 |
Anna C Groner1, Laura Cato1, Jonas de Tribolet-Hardy1, Tiziano Bernasocchi2, Hana Janouskova2, Diana Melchers3, René Houtman3, Andrew C B Cato4, Patrick Tschopp5, Lei Gu6, Andrea Corsinotti7, Qing Zhong8, Christian Fankhauser9, Christine Fritz8, Cédric Poyet10, Ulrich Wagner8, Tiannan Guo11, Ruedi Aebersold12, Levi A Garraway13, Peter J Wild8, Jean-Philippe Theurillat14, Myles Brown15.
Abstract
Androgen receptor (AR) signaling is a key driver of prostate cancer (PC). While androgen-deprivation therapy is transiently effective in advanced disease, tumors often progress to a lethal castration-resistant state (CRPC). We show that recurrent PC-driver mutations in speckle-type POZ protein (SPOP) stabilize the TRIM24 protein, which promotes proliferation under low androgen conditions. TRIM24 augments AR signaling, and AR and TRIM24 co-activated genes are significantly upregulated in CRPC. Expression of TRIM24 protein increases from primary PC to CRPC, and both TRIM24 protein levels and the AR/TRIM24 gene signature predict disease recurrence. Analyses in CRPC cells reveal that the TRIM24 bromodomain and the AR-interacting motif are essential to support proliferation. These data provide a rationale for therapeutic TRIM24 targeting in SPOP mutant and CRPC patients.Entities:
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Year: 2016 PMID： 27238081 PMCID： PMC5124371 DOI： 10.1016/j.ccell.2016.04.012
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743