期刊
CELL METABOLISM
卷 18, 期 5, 页码 726-739出版社
CELL PRESS
DOI: 10.1016/j.cmet.2013.09.013
关键词
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资金
- National Institutes of Health [NS73831, CA151819]
- NIH [P01-CA95616]
- National Foundation for Cancer Research
- Ben & Catherine Ivy Foundation
- Grants-in-Aid for Scientific Research [24791501] Funding Source: KAKEN
Aerobic glycolysis (the Warburg effect) is a core hallmark of cancer, but the molecular mechanisms underlying it remain unclear. Here, we identify an unexpected central role for mTORC2 in cancer metabolic reprogramming where it controls glycolytic metabolism by ultimately regulating the cellular level of c-Myc. We show that mTORC2 promotes inactivating phosphorylation of class IIa histone deacetylases, which leads to the acetylation of FoxO1 and FoxO3, and this in turn releases c-Myc from a suppressive miR-34c-dependent network. These central features of activated mTORC2 signaling, acetylated FoxO, and c-Myc levels are highly intercorrelated in clinical samples and with shorter survival of GBM patients. These results identify a specific, Akt-independent role for mTORC2 in regulating glycolytic metabolism in cancer.
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