TRIM33 drives prostate tumor growth by stabilizing androgen receptor from Skp2-mediated degradation

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Androgen receptor (AR) is a key driver of prostate cancer (PCa) progression.
• AR coregulators significantly influence PCa outcomes.
• Identifying novel AR coactivators is crucial for understanding PCa pathogenesis.

Purpose of the Study:

• To identify novel AR transcriptional coactivators in prostate cancer.
• To elucidate the role of TRIM33 in AR-mediated transcription and PCa progression.
• To evaluate TRIM33 as a potential therapeutic target for PCa.

Main Methods:

• Proteomics approach to identify AR coregulators.
• Chromatin immunoprecipitation (ChIP) assays to assess AR binding.
• Western blotting and ubiquitination assays to study AR protein stability.
• Cell-cycle and apoptosis assays to evaluate TRIM33's role in PCa cell survival.
• Analysis of clinical patient cohorts for TRIM33 expression.

Main Results:

• TRIM33 identified as a novel AR transcriptional coactivator.
• TRIM33 enhances AR chromatin binding and promotes PCa progression-related gene transcription.
• TRIM33 stabilizes AR by inhibiting Skp2-mediated degradation.
• TRIM33 is essential for PCa tumor growth, preventing cell-cycle arrest and apoptosis.
• TRIM33 knockdown sensitizes PCa cells to AR antagonists.
• TRIM33 is upregulated in PCa patient samples.
• An AR-TRIM33-coactivated gene signature predicts PCa recurrence.

Conclusions:

• TRIM33 functions as an oncogenic AR coactivator in prostate cancer.
• TRIM33 plays a critical role in promoting PCa development and progression.
• TRIM33 represents a promising therapeutic target for prostate cancer treatment.