Artículo
The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism
Sebastián, Carlos; Zwaans, Bernardette M. M.; Silberman, Dafne Magali
; Gymrek, Melissa; Goren, Alon; Zhong, Lei; Ram, Oren; Truelove, Jessica; Guimaraes, Alexander R.; Toiber, Debra; Cosentino, Claudia; Greenson, Joel K.; MacDonald, Alasdair I.; McGlynn, Liane; Maxwell, Fraser; Edwards, Joanne; Giacosa, Sofía; Guccione, Ernesto; Weissleder, Ralph; Bernstein, Bradley E.; Regev, Aviv; Shiels, Paul G.; Lombard, David B.; Mostoslavsky, Raul
Fecha de publicación:
12/2012
Editorial:
Elsevier
Revista:
Cell
ISSN:
0092-8674
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
Sirt6
,
Cancer
,
Metabolism
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Colecciones
Articulos(CEFYBO)
Articulos de CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Articulos de CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Citación
Sebastián, Carlos; Zwaans, Bernardette M. M.; Silberman, Dafne Magali; Gymrek, Melissa; Goren, Alon; et al.; The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism; Elsevier; Cell; 151; 6; 12-2012; 1185-1199
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