Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis

  • Hepatology. 2017 Feb;65(2):515-528. doi: 10.1002/hep.28887.
Hongli Hu  1 ,  Wenwei Zhu  2  3 ,  Jun Qin  4 ,  Min Chen  1 ,  Liyan Gong  1 ,  Long Li  1 ,  Xiangyuan Liu  1 ,  Yongzhen Tao  5 ,  Huiyong Yin  5 ,  Hu Zhou  6 ,  Lisha Zhou  7 ,  Dan Ye  7 ,  Qinghai Ye  3 ,  Daming Gao  1
Affiliations
  • 1. CAS Key Laboratory of Systems Biology, Innovation Center for Cell Signaling Network, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
  • 2. Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
  • 3. Liver Cancer Institute & Zhongshan Hospital, Institutes of Biomedical Science, Fudan University, Shanghai, China.
  • 4. Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5. Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
  • 6. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • 7. Key Laboratory of Molecular Medicine of Ministry of Education and Institutes of Biomedical Sciences, Shanghai Medical College, College of Life Science, Fudan University, Shanghai, China.
PMID: 27774669 DOI: 10.1002/hep.28887
Abstract

Phosphoglycerate kinase 1 (PGK1) is an important enzyme in the metabolic glycolysis pathway. In this study, we observed a significant overexpression of PGK1 in liver Cancer tissues and a negative correlation between PGK1 expression and liver Cancer patient survival. Furthermore, depletion of PGK1 dramatically reduced Cancer cell proliferation and tumorigenesis, indicating an oncogenic role of PGK1 in liver Cancer progression. Moreover, we identified acetylation at the K323 site of PGK1 as an important regulatory mechanism for promoting its enzymatic activity and Cancer cell metabolism. And we further characterized P300/cyclic adenosine monophosphate response element binding protein-binding protein-associated factor (PCAF) and Sirtuin 7 as the Enzymes regulating K323 acetylation from both directions in liver Cancer cells.

Conclusion: These findings demonstrate a novel regulation of PGK1 as well as its important role in liver Cancer progression. (Hepatology 2017;65:515-528).