| First Author | Finley LW | Year | 2011 |
| Journal | Cancer Cell | Volume | 19 |
| Issue | 3 | Pages | 416-28 |
| PubMed ID | 21397863 | Mgi Jnum | J:169928 |
| Mgi Id | MGI:4943604 | Doi | 10.1016/j.ccr.2011.02.014 |
| Citation | Finley LW, et al. (2011) SIRT3 Opposes Reprogramming of Cancer Cell Metabolism through HIF1alpha Destabilization. Cancer Cell 19(3):416-28 |
| abstractText | 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-1alpha (HIF1alpha), a transcription factor that controls glycolytic gene expression. SIRT3 loss increases reactive oxygen species production, leading to HIF1alpha stabilization. SIRT3 expression is reduced in human breast cancers, and its loss correlates with the upregulation of HIF1alpha target genes. Finally, we find that SIRT3 overexpression represses glycolysis and proliferation in breast cancer cells, providing a metabolic mechanism for tumor suppression. |
