Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming.
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.
Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
Yoichiro
Y
Mitsuishi
Keiko
K
Taguchi
Yukie
Y
Kawatani
Tatsuhiro
T
Shibata
Toshihiro
T
Nukiwa
Hiroyuki
H
Aburatani
Masayuki
M
Yamamoto
Hozumi
H
Motohashi
D000818:Animals; D002455:Cell Division; D005947:Glucose / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D005973:Glutamine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose