RRC ID 76708
Author Zhou L, Wang Z, Chen X, Li X, Ge C, Min X, Zhao F, Chen T, Li J.
Title Syntaxin-6 promotes the progression of hepatocellular carcinoma and alters its sensitivity to chemotherapies by activating the USF2/LC3B axis.
Journal Int J Biol Sci
Abstract Syntaxin-6 (STX6), a protein of the syntaxin family, is located in the trans-Golgi network and is involved in a variety of intracellular membrane transport events. STX6 is overexpressed in different human malignant tumors. However, little is known about its exact function and molecular mechanism in hepatocellular carcinoma (HCC). In this study, we found that the expression of STX6 was significantly increased in HCC tissues and was associated with poor survival. Gain- and loss-of-function experiments showed that STX6 promotes cell proliferation and metastasis of HCC cells both in vitro and in vivo. Mechanistically, STX6 was negatively regulated by the upstream stimulatory factor 2 (USF2). In addition, STX6 facilitates the association of autophagosomes with lysosomes. Importantly, we demonstrated that STX6 overexpression, despite enhanced resistance to lenvatinib, sensitizes HCC cells to the autophagy activator rapamycin. This study revealed that, under the control of USF2, STX6 accelerates the degradation of microtubule-associated protein 1 light chain 3 beta (LC3) by promoting autophagic flux, ultimately promoting HCC progression. Collectively, we suggest that the USF2-STX6-LC3B axis is a potential therapeutic target in liver cancer.
Volume 19(12)
Pages 3892-3907
Published 2023-1-1
DOI 10.7150/ijbs.86636
PII ijbsv19p3892
PMID 37564208
PMC PMC10411479
MeSH Autophagy / genetics Carcinoma, Hepatocellular* / drug therapy Carcinoma, Hepatocellular* / genetics Carcinoma, Hepatocellular* / metabolism Cell Line Cell Line, Tumor Cell Proliferation / genetics Gene Expression Regulation, Neoplastic Humans Liver Neoplasms* / drug therapy Liver Neoplasms* / genetics Liver Neoplasms* / metabolism Qa-SNARE Proteins / genetics Qa-SNARE Proteins / metabolism Upstream Stimulatory Factors / metabolism
IF 4.858
Human and Animal Cells HuH-7(RCB1366)