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Updated: Feb 9, 2026

A "Patient-Like" Orthotopic Syngeneic Mouse Model of Hepatocellular Carcinoma Metastasis
Published on: October 24, 2015
CD24 regulates sorafenib resistance via activating autophagy in hepatocellular carcinoma
Shuai Lu1,2,3, Yao Yao1,4, Guolong Xu1,2,3
1Department of Immunology, Nanjing Medical University, Nanjing, 211166, China.
Abstract:
Hepatocellular carcinoma is one of most common solid cancers worldwide. Sorafenib is indicated as a treatment for advanced hepatocellular carcinoma (HCC). However, the clinical efficacy of sorafenib has been severely compromised by the development of drug resistance, and the precise mechanisms of drug resistance remain largely unknown. Here we found that a cell surface molecule, CD24, is overexpressed in tumor tissues and sorafenib-resistant hepatocellular carcinoma cell lines. Moreover, there is a positive correlation between CD24 expression levels and sorafenib resistance. In sorafenib-resistant HCC cell lines, depletion of CD24 caused a notable increase of sorafenib sensitivity. In addition, we found that CD24-related sorafenib resistance was accompanied by the activation of autophagy and can be blocked by the inhibition of autophagy using either pharmacological inhibitors or essential autophagy gene knockdown. In further research, we found that CD24 overexpression also leads to an increase in PP2A protein production and induces the deactivation of the mTOR/AKT pathway, which enhances the level of autophagy. These results demonstrate that CD24 regulates sorafenib resistance via activating autophagy in HCC. This is the first report to describe the relationships among CD24, autophagy, and sorafenib resistance. In conclusion, the combination of autophagy modulation and CD24 targeted therapy is a promising therapeutic strategy in the treatment of HCC.
Insights
CD24 overexpression drives sorafenib resistance in hepatocellular carcinoma (HCC) by activating autophagy. Targeting CD24 and autophagy offers a promising strategy for overcoming drug resistance in HCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Hepatocellular carcinoma (HCC) is a prevalent global cancer.
- Sorafenib is a key treatment for advanced HCC, but drug resistance limits its efficacy.
- Mechanisms underlying sorafenib resistance in HCC are not fully understood.
Purpose of the Study:
- To investigate the role of CD24 in sorafenib resistance in HCC.
- To elucidate the molecular mechanisms linking CD24 to sorafenib resistance.
- To explore potential therapeutic strategies targeting CD24 and autophagy.
Main Methods:
- Analysis of CD24 expression in HCC tumor tissues and cell lines.
- Assessment of sorafenib sensitivity in HCC cell lines with varying CD24 levels.
- Investigation of autophagy activation and its modulation by CD24.
- Examination of the mTOR/AKT pathway and PP2A protein in relation to CD24 and autophagy.
Main Results:
- CD24 is overexpressed in HCC tissues and sorafenib-resistant cell lines, correlating positively with resistance.
- CD24 depletion enhances sorafenib sensitivity in resistant HCC cells.
- CD24-mediated resistance involves autophagy activation, which can be inhibited pharmacologically or genetically.
- CD24 overexpression increases PP2A, deactivates mTOR/AKT, and subsequently enhances autophagy.
Conclusions:
- CD24 plays a critical role in regulating sorafenib resistance in HCC through autophagy activation.
- This study establishes a novel link between CD24, autophagy, and sorafenib resistance.
- Combined targeting of CD24 and autophagy modulation presents a promising therapeutic approach for HCC treatment.
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