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Updated: Sep 19, 2025
08:49
Murine Prostate Micro-dissection and Surgical Castration
Published on: May 11, 2016
46.1K
RSK1-driven TRIM28/E2F1 feedback loop promotes castration-resistant prostate cancer progression
Miyeong Kim1, Jinpeng Liu2, Yanquan Zhang1
1Department of Toxicology and Cancer Biology.
The Journal of Clinical Investigation
|June 16, 2025
Summary
Castration-resistant prostate cancer (CRPC) progression is driven by the RSK1-TRIM28-E2F1 axis. Targeting this pathway, particularly TRIM28 phosphorylation, offers a potential vulnerability for treating advanced prostate cancer.
Area of Science:
- Molecular oncology
- Cancer biology
Background:
- Castration-resistant prostate cancer (CRPC) is an advanced, lethal stage of prostate cancer (PCa).
- TRIM28 (KAP1) promotes CRPC cell proliferation and tumor growth, but its regulatory mechanisms and targets in CRPC remain unclear.
Purpose of the Study:
- To elucidate the mechanisms of TRIM28 upregulation in CRPC.
- To identify genomic targets regulated by TRIM28.
- To investigate the role of the RSK1-TRIM28-E2F1 axis in CRPC progression.
Main Methods:
- Integrated genomic analysis to identify TRIM28 as an E2F1 target.
- Investigated TRIM28/E2F1 feedback loop independent of retinoblastoma (Rb) status.
- Identified RSK1 as the kinase phosphorylating TRIM28 at S473.
Main Results:
- TRIM28 is a direct E2F1 target in CRPC, forming a positive feedback loop.
- RSK1 directly phosphorylates TRIM28 (pS473-TRIM28), driving the TRIM28/E2F1 loop.
- pS473-TRIM28 promotes CRPC progression; RSK inhibition mitigates this effect.
Conclusions:
- The RSK1-TRIM28-E2F1 axis is critical for CRPC progression.
- This axis represents a potential therapeutic vulnerability, especially in Rb-deficient CRPC.
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