癌細胞消耗大量的營養(yǎng)，并維持高水平的合成代謝,。最近的研究表明,，各種致癌信號途徑參與調(diào)節(jié)代謝。7月10日,，Cancer Cell雜志報道,，代謝調(diào)節(jié)因子Nrf2通過促進細胞代謝的重新編程加速腫瘤細胞增殖。

Nrf2是維護氧化還原平衡的關(guān)鍵調(diào)節(jié)因子,。它已被證明有助于癌癥的惡性表型,，包括異?；钴S的增殖能力。然而,，Nrf2加速腫瘤細胞增殖的機制尚不完全清楚,。

本研究表明，Nrf2可使葡萄糖和谷氨酰胺重新進入合成代謝途徑,，尤其是在持續(xù)激活PI3K-AKT信號的條件下,。活化的PI3K-Akt通路增強Nrf2在核內(nèi)的積累,，使Nrf2促進那些支持細胞增殖和保護細胞的代謝活動,。 Nrf2的功能性增強還可加強增殖信號觸發(fā)的代謝重新編程。(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.