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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 15, 2011 |
| Title |
SIRT3 opposes metabolic reprogramming of cancer cells through HIF1a destabilization |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Tumor cells exhibit aberrant metabolism characterized by high glycolysis even in the presence of oxygen. This metabolic reprogramming, known as the Warburg effect, provides tumor cells with the substrates and redox potential required for the generation of biomass. Here, we show that the mitochondrial NAD-dependent deacetylase SIRT3 is a crucial regulator of the Warburg effect. SIRT3 loss promotes a metabolic profile consistent with high glycolysis required for anabolic processes in vivo and in vitro. Mechanistically, SIRT3 mediates metabolic reprogramming independently of mitochondrial oxidative metabolism and through HIF1a, a transcription factor that controls expression of key glycolytic enzymes. SIRT3 loss increases reactive oxygen species production, resulting in enhanced HIF1a stabilization. Strikingly, SIRT3 is deleted in 40% of human breast cancers, and its loss correlates with the upregulation of HIF1a target genes. Finally, we find that SIRT3 overexpression directly represses the Warburg effect in breast cancer cells. In sum, we identify SIRT3 as a regulator of HIF1a and a suppressor of the Warburg effect.
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| Overall design |
RNA isolated from brown adipose tissue of SIRT3 WT and KO mice. 5 wild-type samples and 5 SIRT3 KO samples
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| Contributor(s) |
Finley LS, Carracedo A, Lee J, Souza A, Egia A, Zheng J, Teruya-Feldstein J, Moreira PI, Cardoso SM, Clish CB, Pandolfi PP, Haigis MC |
| Citation(s) |
21397863 |
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| Submission date |
Feb 14, 2011 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Marcia C Haigis |
| Organization name |
Harvard Medical School
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| Street address |
77 Ave Louis Pasteur
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA137189 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE27309_RAW.tar |
35.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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