TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer.

Details

Serval ID
serval:BIB_020FBFC9715D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer.
Journal
Cancer cell
Author(s)
Groner A.C., Cato L., de Tribolet-Hardy J., Bernasocchi T., Janouskova H., Melchers D., Houtman R., Cato A.C., Tschopp P., Gu L., Corsinotti A., Zhong Q., Fankhauser C., Fritz C., Poyet C., Wagner U., Guo T., Aebersold R., Garraway L.A., Wild P.J., Theurillat J.P., Brown M.
ISSN
1878-3686 (Electronic)
ISSN-L
1535-6108
Publication state
Published
Issued date
13/04/2016
Peer-reviewed
Oui
Volume
29
Number
6
Pages
846-858
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.

Keywords
Animals, Carrier Proteins/chemistry, Carrier Proteins/genetics, Carrier Proteins/metabolism, Cell Proliferation, Disease Progression, Gene Expression Regulation, Neoplastic, Humans, Male, Neoplasm Transplantation, Nuclear Proteins/genetics, Prostatic Neoplasms/genetics, Prostatic Neoplasms/metabolism, Prostatic Neoplasms/pathology, Prostatic Neoplasms, Castration-Resistant/genetics, Prostatic Neoplasms, Castration-Resistant/metabolism, Prostatic Neoplasms, Castration-Resistant/pathology, Receptors, Androgen/chemistry, Receptors, Androgen/genetics, Receptors, Androgen/metabolism, Repressor Proteins/genetics, Signal Transduction
Pubmed
Open Access
Yes
Create date
14/06/2016 16:15
Last modification date
20/08/2019 12:24
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