Int J Biol Sci 2020; 16(9):1495-1506. doi:10.7150/ijbs.41051 This issue

Review

The Role of D-3-Phosphoglycerate Dehydrogenase in Cancer

Xiaoya Zhao1, Jianfei Fu2, Jinlin Du3✉, Wenxia Xu1✉

1. Central Laboratory, Jinhua Hospital of Zhejiang University, Jinhua 321000, Zhejiang Province, China
2. Department of Medical Oncology, Jinhua Hospital of Zhejiang University, Jinhua 321000, Zhejiang Province, China
3. Department of Colorectal Surgery, Jinhua Hospital of Zhejiang University, Jinhua 321000, Zhejiang Province, China

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Citation:
Zhao X, Fu J, Du J, Xu W. The Role of D-3-Phosphoglycerate Dehydrogenase in Cancer. Int J Biol Sci 2020; 16(9):1495-1506. doi:10.7150/ijbs.41051. Available from https://www.ijbs.com/v16p1495.htm

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Abstract

Graphic 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.

Keywords: serine metabolism, SSP, structure of PHGDH, expression of PHGDH, cancer, non-metabolic activity, inhibitor of PHGDH, tumor resistance