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

作者全名：Liu, Rui; Liu, Yi; Zhang, Wenlu; Zhang, Guiji; Zhang, Zhirong; Huang, Luyi; Tang, Ni; Wang, Kai

作者地址：[Liu, Rui; Liu, Yi; Zhang, Wenlu; Zhang, Zhirong; Huang, Luyi; Tang, Ni; Wang, Kai] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis,Key Lab Mol Biol Infect Dis,Minist, Chongqing 400016, Peoples R China; [Zhang, Guiji] Univ Elect Sci & Technol China, Sichuan Canc Hosp & Inst, Sichuan Clin Res Ctr Canc,Affiliated Canc Hosp, Sichuan Canc Ctr,Dept Clin Lab, Chengdu 610041, Sichuan, Peoples R China

通信作者：Tang, N; Wang, K (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis,Key Lab Mol Biol Infect Dis,Minist, Chongqing 400016, Peoples R China.

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001219419000001

JCR分区：Q1

影响因子：6.9

年份：2024

卷号：11

期号：4

开始页：　

结束页：　

文献类型：Article

关键词：Cancer stem cells; Chemoresistance; Gluconeogenesis; Hepatocellular carcinoma; YAP

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 oncogenesis 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 carcinoma 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 strategy in hepatocellular carcinoma.

基金机构：National Natural Science Foundation of China [82073251, 82303854]; Natural Science Foundation Project of Chongqing, China [cstc2019jcyj-msxmX0587, cstc2019jscx-dxwtBX0019]; Science and Technology Research Program of Chongqing Municipal Education Commission of China [HZ2021006, KJZDM202000401]; Future Medical Youth Innovation Team of Chongqing Medical University [W0036, W0101]; Natural Science Foundation of Sichuan Province [22NSFSC1284]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University

基金资助正文：<BOLD> We are grateful that Prof. Tong-Chuan He (University of Chicago, USA) kindly provided the pAdEasy system. We thank Prof. Ding Xue (Tsinghua University, Beijing, China) for supplying the CRISPR/Cas9 system. </BOLD> This work was 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) , and the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University.