TY - JOUR
T1 - Nrf2 Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming
AU - Mitsuishi, Yoichiro
AU - Taguchi, Keiko
AU - Kawatani, Yukie
AU - Shibata, Tatsuhiro
AU - Nukiwa, Toshihiro
AU - Aburatani, Hiroyuki
AU - Yamamoto, Masayuki
AU - Motohashi, Hozumi
N1 - Funding Information:
We would like to thank Drs. Akihiko Muto, Kai Takaya and Maki Goto for providing us the technical advice and key materials. We also thank Ms. Eriko Naganuma and the Biomedical Research Core of the Tohoku University Graduate School of Medicine for their technical support. This work was supported by Grants-in-Aid for Creative Scientific Research (M.Y.) and Scientific Research (K.T., M.Y., and H.M.) from the JSPS; Grants-in-Aid for Scientific Research on Innovative Areas (K.T., M.Y., and H.M.) from the MEXT; the Tohoku University Global COE for the Conquest of Signal Transduction Diseases with Network Medicine (K.T. and M.Y.); JST, CREST (M.Y. and H.M.); and a research grant from the Princess Takamatsu Cancer Research Fund 09-24118 (H.M.).
PY - 2012/7/10
Y1 - 2012/7/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84863764614&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863764614&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2012.05.016
DO - 10.1016/j.ccr.2012.05.016
M3 - Article
C2 - 22789539
AN - SCOPUS:84863764614
SN - 1535-6108
VL - 22
SP - 66
EP - 79
JO - Cancer Cell
JF - Cancer Cell
IS - 1
ER -
