Hepatocellular carcinoma(HCC)is a common malignancy that is driven by multiple genes and pathways.The aim of this study was to investigate the role and specific mechanism of the actin-interacting protein zyxin(ZYX)in ...Hepatocellular carcinoma(HCC)is a common malignancy that is driven by multiple genes and pathways.The aim of this study was to investigate the role and specific mechanism of the actin-interacting protein zyxin(ZYX)in HCC.We found that the expression of ZYX was significantly higher in HCC tissues compared to that in normal liver tissues.In addition,overexpression of ZYX in hepatoma cell lines(PLC/PRF/5,HCCLM3)enhanced their proliferation,migration and invasion,whereas ZYX knockdown had the opposite effects(SK HEP-1,Huh-7).Furthermore,the change in the expression levels of ZYX also altered that of proteins related to cell cycle,migration and invasion.Similar results were obtained with xenograft models.The AKT/mTOR signaling pathway is one of the key mediators of cancer development.While ZYX overexpression upregulated the levels of phosphorylated AKT/mTOR proteins,its knockdown had the opposite effect.In addition,the AKT inhibitor MK2206 neutralized the pro-oncogenic effects of ZYX on the HCC cells,whereas the AKT activator SC79 restored the proliferation,migration and invasion of HCC cells with ZYX knockdown.Taken together,ZYX promotes the malignant progression of HCC by activating AKT/mTOR signaling pathway,and is a potential therapeutic target in HCC.展开更多
基金supported by the National Natural Science Foundation of China(No.82170587)the National Natural Science Foundation of China(No.82100647)+3 种基金Luzhou Municipal People’s Government-Southwest Medical University Science and Technology Strategic Cooperation Project(No.2021LZXNYD-Z01)Sichuan Province International Science and Technology Innovation Cooperation Project(No.2023YFH0078)Sichuan Science and Technology Program(2022YFS0625)the Talent Development Project of the Affiliated Hospital of Southwest Medical University.
文摘Hepatocellular carcinoma(HCC)is a common malignancy that is driven by multiple genes and pathways.The aim of this study was to investigate the role and specific mechanism of the actin-interacting protein zyxin(ZYX)in HCC.We found that the expression of ZYX was significantly higher in HCC tissues compared to that in normal liver tissues.In addition,overexpression of ZYX in hepatoma cell lines(PLC/PRF/5,HCCLM3)enhanced their proliferation,migration and invasion,whereas ZYX knockdown had the opposite effects(SK HEP-1,Huh-7).Furthermore,the change in the expression levels of ZYX also altered that of proteins related to cell cycle,migration and invasion.Similar results were obtained with xenograft models.The AKT/mTOR signaling pathway is one of the key mediators of cancer development.While ZYX overexpression upregulated the levels of phosphorylated AKT/mTOR proteins,its knockdown had the opposite effect.In addition,the AKT inhibitor MK2206 neutralized the pro-oncogenic effects of ZYX on the HCC cells,whereas the AKT activator SC79 restored the proliferation,migration and invasion of HCC cells with ZYX knockdown.Taken together,ZYX promotes the malignant progression of HCC by activating AKT/mTOR signaling pathway,and is a potential therapeutic target in HCC.
