File Download
There are no files associated with this item.
SFX Link
- Find it @ UNIST can give you direct access to the published full text of this article. (UNISTARs only)
- Chae, Young Chan
- Cancer Translational Research Lab.
Views & Downloads
Detailed Information
Cited time in 
Cited time in 
Cited time in
Metadata Downloads
Mitochondrial Akt Regulation of Hypoxic Tumor Reprogramming
- Author(s)
- Chae, Young Chan, Vaira, Valentina, Caino, M. Cecilia, Tang, Hsin-Yao, Seo, Jae Ho, Kossenkov, Andrew V., Ottobrini, Luisa, Martelli, Cristina, Lucignani, Giovanni, Bertolini, Irene, Locatelli, Marco, Bryant, Kelly G., Ghosh, Jagadish C., Lisanti, Sofia, Ku, Bonsu, Bosari, Silvano, Languino, Lucia R., Speicher, David W., Altieri, Dario C.
- Issued Date
- 2016-08
- Citation
- CANCER CELL, v.30, no.2, pp.257 - 272
- Abstract
- 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 tumormetabolism toward glycolysis, antagonizes apoptosis and autophagy, dampens oxidative stress, and maintains tumor cell proliferation in the face of severe hypoxia. Mitochondrial Akt-PDK1 signaling correlates with unfavorable prognostic markers and shorter survival in glioma patients and may provide an "actionable'' therapeutic target in cancer.
- Publisher
- CELL PRESS
- ISSN
- 1535-6108
Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.