Related Experiment Video
Updated: Jan 10, 2026
06:38
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
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The Rac1-USP11 feedback amplification loop: a radiation-activated engine driving radioresistance in hepatocellular
Kaixiao Zhou1, Yabo Jiang2, Jiahao Guo1
1State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Key Laboratory of Radiation Damage and Treatment of Jiangsu Provincial Universities and Colleges, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China.
British Journal of Cancer
|November 26, 2025
Summary
Researchers discovered a Rac1-USP11 feedback loop that drives hepatocellular carcinoma (HCC) radioresistance. Inhibiting this loop may improve radiotherapy efficacy in HCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy
Background:
- Radioresistance significantly impacts hepatocellular carcinoma (HCC) treatment efficacy.
- The underlying molecular mechanisms of radioresistance in HCC remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular mechanisms driving radioresistance in hepatocellular carcinoma (HCC).
- To identify potential therapeutic targets for overcoming radioresistance in HCC.
Main Methods:
- Integrative analysis of HCC patient data (RNA-seq, IHC).
- Assessment of radiosensitivity in HCC cell lines and xenograft models.
- Investigation of protein interactions, post-translational modifications, and Rac1 activity.
- Functional validation using pharmacological inhibitors and genetic manipulation.
Main Results:
- Elevated activated Rac1 (Rac1-GTP) predicts poor response to radiotherapy.
- Ionizing radiation activates Rac1, promoting USP11 transcription.
- USP11 stabilizes Rac1-GTP via deubiquitination, forming a positive feedback loop that enhances radioresistance.
- Inhibition of the Rac1-USP11 loop, or Rac1 deubiquitination sites, reversed radioresistance.
- Combined inhibition of Rac1-GTP and USP11 demonstrated enhanced radiosensitization.
Conclusions:
- A novel, self-reinforcing Rac1-USP11 feedback loop drives radioresistance in HCC.
- Targeting this loop presents a promising therapeutic strategy for radiosensitizing HCC.
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