丙酮酸脱氢酶激酶4（PDK4）的下调促进脂肪生成并与肝细胞癌的不良预后相关。
Downregulation of PDK4 Increases Lipogenesis and Associates with Poor Prognosis in Hepatocellular Carcinoma.
作者信息
Yang Chen, Wang Siying, Ruan Haoyu, Li Botai, Cheng Zhuoan, He Jia, Zuo Qiaozhu, Yu Chengtao, Wang Hui, Lv Yuanyuan, Gu Dishui, Jin Guangzhi, Yao Ming, Qin Wenxin, Jin Haojie
机构信息
Shanghai Medical College of Fudan University, Shanghai, China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
出版信息
J Cancer. 2019 Jan 29;10(4):918-926. doi: 10.7150/jca.27226. eCollection 2019.
Alterations in cellular metabolism are one of the characteristics in cancer. They are not only the result of tumor progression but also the cause of cancer initiation. Pyruvate dehydrogenase kinase 4 (PDK4) is a key metabolic enzyme, which regulates cell metabolism by inhibiting pyruvate dehydrogenase (PDH). However, the function and regulating mechanism of PDK4 in HCC remain unclear. Here, we found that the expression of PDK4 was significantly decreased in HCC tissues, and its downregulation could predict poor prognosis of HCC patients. Silencing PDK4 significantly facilitated proliferation and migration of HCC cells. Knockdown of PDK4 didn't influence the oxidative phosphorylation and glycolysis capacity of HCC cells . However, knockdown of PDK4 increased expression of key lipogenic enzymes, fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD), which finally induced lipogenesis. These data suggest that PDK4 inhibits proliferation and migration of HCC cells probably via suppressing lipogenesis.
细胞代谢改变是癌症的特征之一。它们不仅是肿瘤进展的结果，也是癌症发生的原因。丙酮酸脱氢酶激酶4（PDK4）是一种关键的代谢酶，通过抑制丙酮酸脱氢酶（PDH）来调节细胞代谢。然而，PDK4在肝癌中的功能和调控机制仍不清楚。在此，我们发现PDK4在肝癌组织中的表达显著降低，其下调可预测肝癌患者的不良预后。沉默PDK4显著促进肝癌细胞的增殖和迁移。敲低PDK4不影响肝癌细胞的氧化磷酸化和糖酵解能力。然而，敲低PDK4增加了关键脂肪生成酶脂肪酸合酶（FASN）和硬脂酰辅酶A去饱和酶（SCD）的表达，最终诱导脂肪生成。这些数据表明，PDK4可能通过抑制脂肪生成来抑制肝癌细胞的增殖和迁移。
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