@article{e2f66d2a4a204fe187a1fef4cb3bc342,
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.",
author = "Kenta Masui and Kazuhiro Tanaka and David Akhavan and Ivan Babic and Beatrice Gini and Tomoo Matsutani and Akio Iwanami and Feng Liu and Villa, {Genaro R.} and Yuchao Gu and Carl Campos and Shaojun Zhu and Huijun Yang and Yong, {William H.} and Cloughesy, {Timothy F.} and Mellinghoff, {Ingo K.} and Cavenee, {Webster K.} and Shaw, {Reuben J.} and Mischel, {Paul S.}",
note = "Funding Information: We thank Dr. Cameron Brennan and Alicia Pedraza (Memorial Sloan-Kettering Cancer Center) for kindly giving us TS516 GBM sphere cell lines; Dr. Ciro Zanca, Tomoyuki Koga, John Anzola, and Yuki Ishii (Ludwig Institute for Cancer Research) for GBM6, GBM39, H1650, A549, and HeLa cell lines; and the UCLA Brain Tumor Translational Resource for biospecimen and biorepository support. A PI3K/mTOR dual inhibitor, XL765 (SAR245409), was kindly provided by Exelixis/Sanofi to I.K.M. This work is supported by grants from the National Institutes of Health (NS73831 and CA151819) (P.S.M.), NIH grant P01-CA95616 and a Fellow award from the National Foundation for Cancer Research (W.K.C.), and The Ben & Catherine Ivy Foundation and generous donations from the Ziering Family Foundation in memory of Sigi Ziering (T.F.C. and P.S.M.). ",
year = "2013",
month = nov,
day = "5",
doi = "10.1016/j.cmet.2013.09.013",
language = "English",
volume = "18",
pages = "726--739",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "5",
}
