Serine Synthesis Helps Hypoxic Cancer Stem Cells Regulate Redox
Serine Synthesis Helps Hypoxic Cancer Stem Cells Regulate Redox
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DOI：
10.1158/0008-5472.can-16-1730
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发表时间：
2016-11-15
期刊：
影响因子：
11.2
通讯作者：
Semenza, Gregg L.
中科院分区：
文献类型：
--
作者：
Samanta, Debangshu;Semenza, Gregg L.
磷酸甘油酸脱氢酶（PHGDH）是负责将糖酵解中间体3-磷酸甘油酸分流到丝氨酸合成途径的代谢酶。在乳腺癌和其他几种类型的癌症中，PHGDH表达增加与患者死亡率相关。早期的研究集中在PHGDH在促进PHGDH基因扩增的小比例乳腺癌细胞增殖中的作用。然而，最近的研究已经揭示了PHGDH和丝氨酸合成途径的下游酶以及一碳代谢酶NADPH的产生和氧化还原稳态的维持的关键作用，这是乳腺癌干细胞响应缺氧或化疗而富集所需的。这些结果提供了乳腺癌中PHGDH过表达的机制，其中PHGDH未被扩增，并且具有改善三阴性乳腺癌对细胞毒性化疗的反应的意义。(C)2016年AACR。
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 metabolismin 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. (C) 2016 AACR.