PDF(Pubmed)
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.
摘要：
发现肝癌干细胞依赖于糖酵解作为优选的代谢程序。磷酸烯醇丙酮酸羧化酶1（PCK1），一种糖异生代谢酶，在肝细胞癌中表达下调，与不良预后密切相关。肿瘤的发生发展与肿瘤干细胞密切相关。目前尚不清楚PCK1缺乏是否会增加肝癌细胞的干性并促进肝细胞癌的发生。在这里，结果表明，PCK1抑制肝癌细胞的自我更新特性，降低了癌症干细胞标志物的mRNA水平，并抑制肿瘤发生。此外，PCK1增加肝癌细胞对索拉非尼的敏感性。此外，我们发现PCK1通过增强YAP的磷酸化和抑制其核转位来激活Hippo通路。维替泊芬降低肝癌细胞的干性，促进索拉非尼的促凋亡作用。因此，维替泊芬和索拉非尼联合治疗可能是肝细胞癌的潜在抗肿瘤策略.
