Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses.
Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses.
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DOI：
10.1126/science.1211485
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发表时间：
2011-12-02
期刊：
影响因子：
--
通讯作者：
Cantley LC
中科院分区：
文献类型：
--
作者：
Anastasiou D;Poulogiannis G;Asara JM;Boxer MB;Jiang JK;Shen M;Bellinger G;Sasaki AT;Locasale JW;Auld DS;Thomas CJ;Vander Heiden MG;Cantley LC
细胞内活性氧（ROS）浓度的控制对于癌细胞存活至关重要。我们发现，在人肺癌细胞中，细胞内ROS浓度的急剧增加通过Cys358的氧化引起糖酵解酶丙酮酸激酶M2（PKM2）的抑制。PKM2的这种抑制是将葡萄糖流量转移到戊糖磷酸途径中所必需的，从而产生足够的还原潜力用于ROS的解毒。在异种移植模型中，内源性PKM2被Cys358至Ser358抗氧化突变体取代的肺癌细胞表现出对氧化应激的敏感性增加和肿瘤形成受损。除了促进增殖所需的代谢变化外，PKM2的调节特性可能通过允许癌细胞承受氧化应激而赋予癌细胞额外的优势。
Control of intracellular reactive oxygen species (ROS) concentrations is critical for cancer cell survival. We show that, in human lung cancer cells, acute increases in intracellular concentrations of ROS caused inhibition of the glycolytic enzyme pyruvate kinase M2 (PKM2) through oxidation of Cys358. This inhibition of PKM2 is required to divert glucose flux into the pentose phosphate pathway and thereby generate sufficient reducing potential for detoxification of ROS. Lung cancer cells in which endogenous PKM2 was replaced with the Cys358 to Ser358 oxidation-resistant mutant exhibited increased sensitivity to oxidative stress and impaired tumor formation in a xenograft model. Besides promoting metabolic changes required for proliferation, the regulatory properties of PKM2 may confer an additional advantage to cancer cells by allowing them to withstand oxidative stress.
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影响因子：
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作者：
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