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

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

  • Genes Dis. 2023 Sep 16;11(4):101114. doi: 10.1016/j.gendis.2023.101114.
Rui Liu 1,  Yi Liu 1,  Wenlu Zhang 1,  Guiji Zhang 2,  Zhirong Zhang 1,  Luyi Huang 1,  Ni Tang 1,  Kai Wang 1
Affiliations

Affiliations

  • 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.
PMID: 38560500 DOI: 10.1016/j.gendis.2023.101114
Abstract

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.

Keywords

Cancer stem cells; Chemoresistance; Gluconeogenesis; Hepatocellular carcinoma; YAP.

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