TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer.
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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
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Journal | Cancer Cell
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Volume | 29
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Issue | 6
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Pages | 846-58
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Date Published | 2016 06 13
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ISSN | 1878-3686
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URL | |
DOI | 10.1016/j.ccell.2016.04.012
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PubMed ID | 27238081
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PubMed Central ID | PMC5124371
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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
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