TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer

Published on Jun 13, 2016in Cancer Cell26.602
· DOI :10.1016/J.CCELL.2016.04.012
Anna C. Groner16
Estimated H-index: 16
(Harvard University),
Laura Cato9
Estimated H-index: 9
(Harvard University)
+ 19 AuthorsMyles Brown113
Estimated H-index: 113
(Harvard University)
Sources
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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