The Role of D-3-Phosphoglycerate Dehydrogenase in Cancer
Xiaoya Zhao, Jianfei Fu, Jinlin Du, Wenxia Xu
Abstract
Serine, a non-essential amino acid, can be imported from the extracellular environment by transporters and de novo synthesized from glycolytic 3-phosphoglycerate (3-PG) in the serine biosynthetic pathway (SSP). It has been reported that active serine synthesis might be needed for the synthesis of proteins, lipids, and nucleotides and the balance of folate metabolism and redox homeostasis, which are necessary for cancer cell proliferation. Human D-3-phosphoglycerate dehydrogenase (PHGDH), the first and only rate-limiting enzyme in the de novo serine biosynthetic pathway, catalyzes the oxidation of 3-PG derived from glycolysis to 3-phosphohydroxypyruvate (3-PHP). PHGDH is highly expressed in tumors as a result of amplification, transcription, or its degradation and stability alteration, which dysregulates the serine biosynthesis pathway via metabolic enzyme activity to nourish tumors. And some recent researches reported that PHGDH promoted some tumors growth via non-metabolic way by upregulating target cancer-promoting genes. In this article, we reviewed the type, structure, expression and inhibitors of PHGDH, as well as the role it plays in cancer and tumor resistance to chemotherapy.