J Cancer 2019; 10(4):918-926. doi:10.7150/jca.27226 This issue

Research Paper

Downregulation of PDK4 Increases Lipogenesis and Associates with Poor Prognosis in Hepatocellular Carcinoma

Chen Yang1,2*, Siying Wang2*, Haoyu Ruan1, Botai Li3, Zhuoan Cheng3, Jia He2, Qiaozhu Zuo2, Chengtao Yu3, Hui Wang2, Yuanyuan Lv2, Dishui Gu4, Guangzhi Jin5, Ming Yao2, Wenxin Qin2, Haojie Jin2✉

1. Shanghai Medical College of Fudan University, Shanghai, China
2. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
3. School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
4. Department of Pathophysiology, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, Guangdong, 523808, China.
5. Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, China.
*Equal contributors.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Yang C, Wang S, Ruan H, Li B, Cheng Z, He J, Zuo Q, Yu C, Wang H, Lv Y, Gu D, Jin G, Yao M, Qin W, Jin H. Downregulation of PDK4 Increases Lipogenesis and Associates with Poor Prognosis in Hepatocellular Carcinoma. J Cancer 2019; 10(4):918-926. doi:10.7150/jca.27226. Available from https://www.jcancer.org/v10p0918.htm

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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 in vitro. 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.

Keywords: hepatocellular carcinoma, PDK4, proliferation, migration, lipogenesis