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

Research output: Contribution to journalArticlepeer-review

710 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)66-79
Number of pages14
JournalCancer Cell
Volume22
Issue number1
DOIs
Publication statusPublished - 2012 Jul 10

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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