期刊
JOURNAL OF CANCER
卷 10, 期 4, 页码 918-926出版社
IVYSPRING INT PUBL
DOI: 10.7150/jca.27226
关键词
hepatocellular carcinoma; PDK4; proliferation; migration; lipogenesis
类别
资金
- Shanghai Natural Science Foundation of China [16ZR1434700]
- National Key Basic Research Program of China (973 Program) [2015CB553905]
- National Natural Science Foundation of China [81702838]
- Shanghai Jiao Tong University School of Medicine [PYII-17-013, YG2015QN34]
- Shanghai Municipal Commission of Health and Family Planning [201640055, 2018YQ20]
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.
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