PCK1 attenuates tumor stemness via activating the Hippo signaling pathway in hepatocellular carcinoma

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外文摘要：Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic program.Phosphoenolpyruvate carboxylase 1(PCK1),a gluconeogenic metabolic enzyme,is down-regulated in hepatocellular carcinoma and is closely related to poor prognosis.The onco-genesis and progression of tumors are closely related to cancer stem cells.It is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular carcinoma.Herein,the results showed that PCK1 inhibited the self-renewal property of hepatoma cells,reduced the mRNA level of cancer stem cell markers,and inhibited tumorigenesis.Moreover,PCK1 increased the sensitivity of hepatocellular carci-noma cells to sorafenib.Furthermore,we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear translocation.Verteporfin reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of sorafenib.Thus,combined treatment with verteporfin and sorafenib may be a potential anti-tumor strat-egy in hepatocellular carcinoma.

外文关键词：

Cancer stem cellsChemoresistanceGluconeogenesisHepatocellular carcinomaYAP

作者：

Rui Liu、Yi Liu、Wenlu Zhang、Guiji Zhang、Zhirong Zhang、Luyi Huang、Ni Tang、Kai Wang

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作者单位：

Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education),Institute for Viral Hepatitis,Department of Infectious Diseases,The Second Affiliated Hospital,Chongqing Medical University,Chongqing 400016,China

Department of Clinical Laboratory,Sichuan Clinical Research Center for Cancer,Sichuan Cancer Hospital & Institute,Sichuan Cancer Center,Affiliated Cancer Hospital of University of Electronic Science and Technology of China,Chengdu,Sichuan 610041,China

基金：

国家自然科学基金国家自然科学基金Natural Science Foundation Project of Chongqing,ChinaNatural Science Foundation Project of Chongqing,ChinaScience and Technology Research Program of Chongqing Municipal Education Commission of ChinaScience and Technology Research Program of Chongqing Municipal Education Commission of ChinaFuture Medical Youth Innovation Team of Chongqing Medical UniversityFuture Medical Youth Innovation Team of Chongqing Medical University四川省自然科学基金Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University

项目编号：

8207325182303854cstc2019jcyjmsxmX0587cstc2019jscxdxwtBX0019HZ2021006KJZDM202000401W0036W010122NSFSC1284

出版年：

2024

DOI：

10.1016/j.gendis.2023.101114

基因与疾病(英文)

ISSN：

年,卷(期)：2024.11(4)