TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2016 May 31

PMID 27238081

Citations 150

Authors

Anna C Groner

Laura Cato

Jonas de Tribolet-Hardy

Tiziano Bernasocchi

Hana Janouskova

Diana Melchers

Rene Houtman

Andrew C B Cato

Patrick Tschopp

Lei Gu

Andrea Corsinotti

Qing Zhong

Christian Fankhauser

Christine Fritz

Cedric Poyet

Ulrich Wagner

Tiannan Guo

Ruedi Aebersold

Levi A Garraway

Peter J Wild

Jean-Philippe Theurillat

Myles Brown

Affiliations

Soon will be listed here.

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.

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