MTOR complex 2 controls glycolytic metabolism in glioblastoma through FoxO acetylation and upregulation of c-Myc Journal Article


Authors: Masui, K.; Tanaka, K.; Akhavan, D.; Babic, I.; Gini, B.; Matsutani, T.; Iwanami, A.; Liu, F.; Villa, G. R.; Gu, Y.; Campos, C.; Zhu, S.; Yang, H.; Yong, W. H.; Cloughesy, T. F.; Mellinghoff, I. K.; Cavenee, W. K.; Shaw, R. J.; Mischel, P. S.
Article Title: MTOR complex 2 controls glycolytic metabolism in glioblastoma through FoxO acetylation and upregulation of c-Myc
Abstract: 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. © 2013 Elsevier Inc.
Journal Title: Cell Metabolism
Volume: 18
Issue: 5
ISSN: 1550-4131
Publisher: Elsevier Inc.  
Date Published: 2013-11-05
Start Page: 726
End Page: 739
Language: English
DOI: 10.1016/j.cmet.2013.09.013
PROVIDER: scopus
PMCID: PMC3840163
PUBMED: 24140020
DOI/URL:
Notes: --- - "Export Date: 2 December 2013" - "Source: Scopus"
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  1. Carl Campos
    24 Campos