TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer

Anna C Groner1, Laura Cato1, Jonas de Tribolet-Hardy1

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

Cancer Cell
|May 31, 2016
PubMed

Insights

Speckle-type POZ protein (SPOP) mutations in prostate cancer (PC) stabilize TRIM24, promoting cancer growth. Targeting TRIM24 offers a new therapeutic strategy for castration-resistant prostate cancer (CRPC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Androgen receptor (AR) signaling drives prostate cancer (PC) progression.
  • Androgen-deprivation therapy is often transiently effective, leading to castration-resistant prostate cancer (CRPC).
  • Speckle-type POZ protein (SPOP) mutations are recurrent drivers in PC.

Purpose of the Study:

  • To investigate the role of TRIM24 in SPOP-mutant prostate cancer.
  • To determine the therapeutic potential of targeting TRIM24 in CRPC.

Main Methods:

  • Analysis of TRIM24 protein levels in primary PC and CRPC tissues.
  • Investigating the functional interaction between SPOP, TRIM24, and AR signaling.
  • Assessing the impact of TRIM24 inhibition on CRPC cell proliferation.

Main Results:

  • SPOP mutations stabilize TRIM24, enhancing AR signaling and promoting proliferation in low androgen conditions.
  • AR and TRIM24 co-activated genes are significantly upregulated in CRPC.
  • TRIM24 protein expression increases from primary PC to CRPC.
  • TRIM24 levels and an AR/TRIM24 gene signature predict disease recurrence.
  • TRIM24's bromodomain and AR-interacting motif are essential for CRPC cell proliferation.

Conclusions:

  • TRIM24 is a key mediator in SPOP-mutant CRPC progression.
  • TRIM24 represents a promising therapeutic target for SPOP-mutant and CRPC patients.

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