癌细胞消耗大量的营养，并维持高水平的合成代谢。最近的研究表明，各种致癌信号途径参与调节代谢。7月10日，Cancer Cell杂志报道，代谢调节因子Nrf2通过促进细胞代谢的重新编程加速肿瘤细胞增殖。
Nrf2是维护氧化还原平衡的关键调节因子。它已被证明有助于癌症的恶性表型，包括异常活跃的增殖能力。然而，Nrf2加速肿瘤细胞增殖的机制尚不完全清楚。
本研究表明，Nrf2可使葡萄糖和谷氨酰胺重新进入合成代谢途径，尤其是在持续激活PI3K-AKT信号的条件下。活化的PI3K-Akt通路增强Nrf2在核内的积累，使Nrf2促进那些支持细胞增殖和保护细胞的代谢活动。 Nrf2的功能性增强还可加强增殖信号触发的代谢重新编程。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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Nrf2 Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming
Yoichiro Mitsuishi, Keiko Taguchi, Yukie Kawatani, Tatsuhiro Shibata, Toshihiro Nukiwa, Hiroyuki Aburatani, Masayuki Yamamoto, Hozumi Motohashi
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.
