Mitochondrial Akt Regulation of Hypoxic Tumor Reprogramming.
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ABSTRACT:
SUBMITTER: Chae YC
PROVIDER: S-EPMC5131882 | biostudies-literature | 2016 Aug
REPOSITORIES: biostudies-literature
Publications
Mitochondrial Akt Regulation of Hypoxic Tumor Reprogramming.
Chae Young Chan YC Vaira Valentina V Caino M Cecilia MC Tang Hsin-Yao HY Seo Jae Ho JH Kossenkov Andrew V AV Ottobrini Luisa L Martelli Cristina C Lucignani Giovanni G Bertolini Irene I Locatelli Marco M Bryant Kelly G KG Ghosh Jagadish C JC Lisanti Sofia S Ku Bonsu B Bosari Silvano S Languino Lucia R LR Speicher David W DW Altieri Dario C DC
Cancer cell 20160801 2
Hypoxia is a universal driver of aggressive tumor behavior, but the underlying mechanisms are not completely understood. Using a phosphoproteomics screen, we now show that active Akt accumulates in the mitochondria during hypoxia and phosphorylates pyruvate dehydrogenase kinase 1 (PDK1) on Thr346 to inactivate the pyruvate dehydrogenase complex. In turn, this pathway switches tumor metabolism toward glycolysis, antagonizes apoptosis and autophagy, dampens oxidative stress, and maintains tumor ce ...[more]
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