TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer.

Cancer Cell
Authors
Keywords
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.

Year of Publication
2016
Journal
Cancer Cell
Volume
29
Issue
6
Pages
846-58
Date Published
2016 06 13
ISSN
1878-3686
URL
DOI
10.1016/j.ccell.2016.04.012
PubMed ID
27238081
PubMed Central ID
PMC5124371
Links
Grant list
P01 CA163227 / CA / NCI NIH HHS / United States
P50 CA090381 / CA / NCI NIH HHS / United States
T32 CA009172 / CA / NCI NIH HHS / United States