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CD24 regulates sorafenib resistance via activating autophagy in hepatocellular carcinoma

Lu, Shuai ; Yao, Yao ; Xu, Guolong ; Zhou, Chao ; Zhang, Yuan ; Sun, Jie ; Jiang, Runqiu ; Shao, Qing ; Chen, Yun

Cell death & disease, 2018-05, Vol.9 (6), p.646-13, Article 646 [Periódico revisado por pares]

England: Springer Nature B.V

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Título:
CD24 regulates sorafenib resistance via activating autophagy in hepatocellular carcinoma
Autor: Lu, Shuai ; Yao, Yao ; Xu, Guolong ; Zhou, Chao ; Zhang, Yuan ; Sun, Jie ; Jiang, Runqiu ; Shao, Qing ; Chen, Yun
Assuntos: AKT protein ; Animals ; Autophagy ; Autophagy - drug effects ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - pathology ; CD24 Antigen - metabolism ; Cell Line, Tumor ; Cell surface ; Deactivation ; Drug resistance ; Drug Resistance, Neoplasm - drug effects ; Female ; Gene Expression Regulation, Neoplastic - drug effects ; Hepatocellular carcinoma ; Humans ; Liver cancer ; Liver Neoplasms - drug therapy ; Liver Neoplasms - genetics ; Liver Neoplasms - pathology ; Mice, Nude ; Phagocytosis ; Prognosis ; Protein Phosphatase 2 - metabolism ; Proto-Oncogene Proteins c-akt - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Signal Transduction ; Sorafenib - pharmacology ; Sorafenib - therapeutic use ; TOR protein ; TOR Serine-Threonine Kinases ; Tumor cell lines ; Vacuoles - drug effects ; Vacuoles - metabolism ; Vacuoles - ultrastructure
É parte de: Cell death & disease, 2018-05, Vol.9 (6), p.646-13, Article 646
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SourceType-Scholarly Journals-1
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Descrição: 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.
Editor: England: Springer Nature B.V
Idioma: Inglês

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CD24 regulates sorafenib resistance via activating autophagy in hepatocellular carcinoma

Lu, Shuai ; Yao, Yao ; Xu, Guolong ; Zhou, Chao ; Zhang, Yuan ; Sun, Jie ; Jiang, Runqiu ; Shao, Qing ; Chen, Yun

England: Springer Nature B.V

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