| First Author | Sebastián C | Year | 2012 |
| Journal | Cell | Volume | 151 |
| Issue | 6 | Pages | 1185-99 |
| PubMed ID | 23217706 | Mgi Jnum | J:219058 |
| Mgi Id | MGI:5619441 | Doi | 10.1016/j.cell.2012.10.047 |
| Citation | Sebastian C, et al. (2012) The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell 151(6):1185-99 |
| abstractText | Reprogramming of cellular metabolism is a key event during tumorigenesis. Despite being known for decades (Warburg effect), the molecular mechanisms regulating this switch remained unexplored. Here, we identify SIRT6 as a tumor suppressor that regulates aerobic glycolysis in cancer cells. Importantly, loss of SIRT6 leads to tumor formation without activation of known oncogenes, whereas transformed SIRT6-deficient cells display increased glycolysis and tumor growth, suggesting that SIRT6 plays a role in both establishment and maintenance of cancer. By using a conditional SIRT6 allele, we show that SIRT6 deletion in vivo increases the number, size, and aggressiveness of tumors. SIRT6 also functions as a regulator of ribosome metabolism by corepressing MYC transcriptional activity. Lastly, Sirt6 is selectively downregulated in several human cancers, and expression levels of SIRT6 predict prognosis and tumor-free survival rates, highlighting SIRT6 as a critical modulator of cancer metabolism. Our studies reveal SIRT6 to be a potent tumor suppressor acting to suppress cancer metabolism. |
