Serine Synthesis Helps Hypoxic Cancer Stem Cells Regulate Redox.
Phosphoglycerate dehydrogenase (PHGDH) is the metabolic enzyme responsible for shunting the glycolytic intermediate 3-phosphoglycerate to the serine synthesis pathway. In breast cancer and several other types of cancer, increased PHGDH expression is associated with patient mortality. Early studies focused on the role of PHGDH in promoting cell proliferation in the small percentage of breast cancers with PHGDH gene amplification. However, recent studies have revealed a critical role for PHGDH and downstream enzymes of the serine synthesis pathway and one carbon metabolism in NADPH production and the maintenance of redox homeostasis, which are required for enrichment of breast cancer stem cells in response to hypoxia or chemotherapy. These results provide a mechanism for PHGDH overexpression in breast cancers in which PHGDH is not amplified and have implications for improving the response of triple-negative breast cancers to cytotoxic chemotherapy. Cancer Res; 76(22); 6458-62. ©2016 AACR.
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland.|McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Debangshu
D
Samanta
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland. gsemenza@jhmi.edu.|McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Departments of Pediatrics, Medicine, Radiation Oncology, and Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Gregg L
GL
Semenza
D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism; D010084:Oxidation-Reduction; D012694:Serine / Q000378:metabolism*
D012694:Serine