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Nrf2 Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming

机译:Nrf2将葡萄糖和谷氨酰胺重定向到代谢重编程中的合成代谢途径。

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Cancer cells consume large quantities of nutrients and maintain high levels of anabolism. Recent studies revealed that various oncogenic pathways are involved in modulation of metabolism. Nrf2, a key regulator for the maintenance of redox homeostasis, has been shown to contribute to malignant phenotypes of cancers including aggressive proliferation. However, the mechanisms with which Nrf2 accelerates proliferation are not fully understood. Here, we show that Nrf2 redirects glucose and glutamine into anabolic pathways, especially under the sustained activation of PI3K-Akt signaling. The active PI3K-Akt pathway augments the nuclear accumulation of Nrf2 and enables Nrf2 to promote metabolic activities that support cell proliferation in addition to enhancing cytoprotection. The functional expansion of Nrf2 reinforces the metabolic reprogramming triggered by proliferative signals.
机译:癌细胞消耗大量营养,并保持高水平的合成代谢。最近的研究表明,各种致癌途径都参与了新陈代谢的调节。 Nrf2是维持氧化还原稳态的关键调节剂,已被证明有助于癌症的恶性表型,包括侵袭性增殖。但是,尚未完全了解Nrf2促进增殖的机制。在这里,我们显示Nrf2将葡萄糖和谷氨酰胺重定向到合成代谢途径,尤其是在PI3K-Akt信号的持续激活下。活跃的PI3K-Akt途径增加了Nrf2的核积累,并使Nrf2能够促进代谢活性,从而除了增强细胞保护作用外还支持细胞增殖。 Nrf2的功能扩展加强了由增殖信号触发的代谢重编程。

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