The histone deacetylase SIRT6 is a novel tumor suppressor that controls cancer metabolism

Sebastián, C. et al. (2012) The histone deacetylase SIRT6 is a novel tumor suppressor that controls cancer metabolism. Cell, 151(6), pp. 1185-1199. (doi: 10.1016/j.cell.2012.10.047) (PMID:23217706) (PMCID:PMC3526953)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McGlynn, Dr Liane and Edwards, Professor Joanne and MacDonald, Dr Alasdair and Maxwell, Dr Fraser and Shiels, Professor Paul
Authors: Sebastián, C., Zwaans, B., Silberman, D.M., Gymrek, M.A., Goren, A., Zhong, L., Ram, O., Truelove, J., Guimaraes, A., Toiber, D., Cosentino, C., Greenson, J., MacDonald, A.I., McGlynn, L., Maxwell, F., Edwards, J., Giacosa, S., Guccione, E., Weissleder, R., Regev, A., Bernstein, B.E., Shiels, P.G., Lombard, D., and Mostoslavsky, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Public Health
Journal Name:Cell
Publisher:Elsevier (Cell Press)
ISSN (Online):1097-4172
Published Online:06 December 2012

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