Gluconeogenesis in Cancer: Function and Regulation of PEPCK, FBPase, and G6Pase
- Trends Cancer. 2019 Jan;5(1):30-45. doi: 10.1016/j.trecan.2018.11.003.
- 1. Department of Pathology and Pathophysiology, and Department of Surgical Oncology (Breast Center) of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Zhejiang Key Laboratory for Disease Proteomics, Zhejiang University School of Medicine, Hangzhou 310058, China.
- 2. Department of Pathology and Pathophysiology, and Department of Surgical Oncology (Breast Center) of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Zhejiang Key Laboratory for Disease Proteomics, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address: [email protected].
Cancer cells display a high rate of glycolysis in the presence of oxygen to promote proliferation. Gluconeogenesis, the reverse pathway of glycolysis, can antagonize aerobic glycolysis in Cancer via three key Enzymes - phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-bisphosphatase (FBPase), and glucose-6-phosphatase (G6Pase). Recent studies have revealed that, in addition to metabolic regulation, these Enzymes also play a role in signaling, proliferation, and the Cancer stem cell (CSC) tumor phenotype. Multifaceted regulation of PEPCK, FBPase, and G6Pase through transcription, Epigenetics, post-translational modification, and enzymatic activity is observed in different cancers. We review here the function and regulation of key gluconeogenic Enzymes and new therapeutic opportunities.