CD24 regulates sorafenib resistance via activating autophagy in hepatocellular carcinoma

Cell Death & Disease
Shuai LuYun Chen

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 ...Continue Reading

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Datasets Mentioned

BETA
E-MTAB-6346

Methods Mentioned

BETA
RNA-seq
fluorescence assay
transmission electron microscopy
gene knockdown
surgical resection
fluorescence microscopy
PCR
xenograft
flow cytometry

Software Mentioned

HiSeq Control Software ( HCS ) OLB
ArrayExpress

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