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

作　　者：Rui Liu Yi Liu Wenlu Zhang Guiji Zhang Zhirong Zhang Luyi Huang Ni Tang Kai Wang 

机构地区：[1]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 [2]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

出　　处：《Genes & Diseases》2024年第4期340-352,共13页基因与疾病（英文）

基　　金：supported by the National Natural Science Foundation of China(No.82073251,82303854);the Natural Science Foundation Project of Chongqing,China(No.cstc2019jcyj-msxmX0587,cstc2019jscx-dxwtBX0019);the Science and Technology Research Program of Chongqing Municipal Education Commission of China(No.HZ2021006,KJZDM202000401);the Future Medical Youth Innovation Team of Chongqing Medical University(No.W0036,W0101);the Natural Science Foundation of Sichuan Province(No.22NSFSC1284);the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University.

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.

关 键 词：Cancer stem cells CHEMORESISTANCE GLUCONEOGENESIS Hepatocellular carcinoma YAP 

分 类 号：R735.7[医药卫生—肿瘤]