SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization Journal Article
| Authors: | Finley, L.; Carracedo, A.; Lee, J.; Souza, A.; Egia, A.; Zhang, J.; Teruya-Feldstein, J.; Moreira, P.; Cardoso, S.; Clish, C.; Pandolfi, P.; Haigis, M. |
| Article Title: | SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization |
| Abstract: | 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 required for biomass generation. Here, we show that the mitochondrial NAD-dependent deacetylase SIRT3 is a crucial regulator of the Warburg effect. Mechanistically, SIRT3 mediates metabolic reprogramming by destabilizing hypoxia-inducible factor-1α (HIF1α), a transcription factor that controls glycolytic gene expression. SIRT3 loss increases reactive oxygen species production, leading to HIF1α stabilization. SIRT3 expression is reduced in human breast cancers, and its loss correlates with the upregulation of HIF1α target genes. Finally, we find that SIRT3 overexpression represses glycolysis and proliferation in breast cancer cells, providing a metabolic mechanism for tumor suppression. © 2011 Elsevier Inc. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; nonhuman; cell proliferation; mouse; animal tissue; breast cancer; animal experiment; animal model; cancer inhibition; correlation analysis; cancer cell; reactive oxygen metabolite; upregulation; tumor growth; hypoxia inducible factor 1alpha; cell metabolism; glycolysis; acyltransferase; nicotinamide adenine dinucleotide; mitochondrial respiration; deacetylase; sirtuin 3 |
| Journal Title: | Cancer Cell |
| Volume: | 19 |
| Issue: | 3 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2011-03-08 |
| Start Page: | 416 |
| End Page: | 428 |
| Language: | English |
| DOI: | 10.1016/j.ccr.2011.02.014 |
| PROVIDER: | scopus |
| PMCID: | PMC3065720 |
| PUBMED: | 21397863 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 23 June 2011" - "CODEN: CCAEC" - "Source: Scopus" |
