Serine synthesis helps hypoxic cancer stem cells regulate redox

Debangshu Samanta, Gregg L. Semenza

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6458-6462
Number of pages5
JournalCancer Research
Volume76
Issue number22
DOIs
StatePublished - Nov 15 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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