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

Autores: 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
Año de publicación: 2012
Idioma: inglés
Tipo de recurso: artículo
Estado: versión publicada
Descripción: 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.
Fil: Sebastián, Carlos. Harvard Medical School; Estados Unidos
Fil: Zwaans, Bernardette M. M.. University of Michigan; Estados Unidos
Fil: Silberman, Dafne Magali. Harvard Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Gymrek, Melissa. Massachusetts Institute of Technology; Estados Unidos
Fil: Goren, Alon. Harvard Medical School; Estados Unidos. Massachusetts Institute of Technology; Estados Unidos
Fil: Zhong, Lei. Harvard Medical School; Estados Unidos
Fil: Ram, Oren. Harvard Medical School; Estados Unidos. Massachusetts Institute of Technology; Estados Unidos
Fil: Truelove, Jessica. The Massachusetts General Hospital; Estados Unidos
Fil: Guimaraes, Alexander R.. The Massachusetts General Hospital; Estados Unidos
Fil: Toiber, Debra. Harvard Medical School; Estados Unidos
Fil: Cosentino, Claudia. Harvard Medical School; Estados Unidos
Fil: Greenson, Joel K.. University of Michigan; Estados Unidos
Fil: MacDonald, Alasdair I.. University of Glasgow; Reino Unido
Fil: McGlynn, Liane. University of Glasgow; Reino Unido
Fil: Maxwell, Fraser. University of Glasgow; Reino Unido
Fil: Edwards, Joanne. University of Glasgow; Reino Unido
Fil: Giacosa, Sofía. Harvard Medical School; Estados Unidos
Fil: Guccione, Ernesto. Institute of Molecular and Cell Biology; Singapur
Fil: Weissleder, Ralph. The Massachusetts General Hospital; Estados Unidos
Fil: Bernstein, Bradley E.. Harvard Medical School; Estados Unidos
Fil: Regev, Aviv. Harvard Medical School; Estados Unidos
Fil: Shiels, Paul G.. University of Glasgow; Reino Unido
Fil: Lombard, David B.. University of Michigan; Estados Unidos
Fil: Mostoslavsky, Raul. Harvard Medical School; Estados Unidos
Materia: Sirt6
Cancer
Metabolism
Nivel de accesibilidad: acceso abierto
Condiciones de uso: https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
Institución: Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador: oai:ri.conicet.gov.ar:11336/17712

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spelling	The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolismSebastián, CarlosZwaans, Bernardette M. M.Silberman, Dafne MagaliGymrek, MelissaGoren, AlonZhong, LeiRam, OrenTruelove, JessicaGuimaraes, Alexander R.Toiber, DebraCosentino, ClaudiaGreenson, Joel K.MacDonald, Alasdair I.McGlynn, LianeMaxwell, FraserEdwards, JoanneGiacosa, SofíaGuccione, ErnestoWeissleder, RalphBernstein, Bradley E.Regev, AvivShiels, Paul G.Lombard, David B.Mostoslavsky, RaulSirt6CancerMetabolismhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Reprogramming 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.Fil: Sebastián, Carlos. Harvard Medical School; Estados UnidosFil: Zwaans, Bernardette M. M.. University of Michigan; Estados UnidosFil: Silberman, Dafne Magali. Harvard Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Gymrek, Melissa. Massachusetts Institute of Technology; Estados UnidosFil: Goren, Alon. Harvard Medical School; Estados Unidos. Massachusetts Institute of Technology; Estados UnidosFil: Zhong, Lei. Harvard Medical School; Estados UnidosFil: Ram, Oren. Harvard Medical School; Estados Unidos. Massachusetts Institute of Technology; Estados UnidosFil: Truelove, Jessica. The Massachusetts General Hospital; Estados UnidosFil: Guimaraes, Alexander R.. The Massachusetts General Hospital; Estados UnidosFil: Toiber, Debra. Harvard Medical School; Estados UnidosFil: Cosentino, Claudia. Harvard Medical School; Estados UnidosFil: Greenson, Joel K.. University of Michigan; Estados UnidosFil: MacDonald, Alasdair I.. University of Glasgow; Reino UnidoFil: McGlynn, Liane. University of Glasgow; Reino UnidoFil: Maxwell, Fraser. University of Glasgow; Reino UnidoFil: Edwards, Joanne. University of Glasgow; Reino UnidoFil: Giacosa, Sofía. Harvard Medical School; Estados UnidosFil: Guccione, Ernesto. Institute of Molecular and Cell Biology; SingapurFil: Weissleder, Ralph. The Massachusetts General Hospital; Estados UnidosFil: Bernstein, Bradley E.. Harvard Medical School; Estados UnidosFil: Regev, Aviv. Harvard Medical School; Estados UnidosFil: Shiels, Paul G.. University of Glasgow; Reino UnidoFil: Lombard, David B.. University of Michigan; Estados UnidosFil: Mostoslavsky, Raul. Harvard Medical School; Estados UnidosElsevier2012-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/17712Sebastián, 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; 1185-11990092-8674enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0092867412013517info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2012.10.047info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:02:40Zoai:ri.conicet.gov.ar:11336/17712instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:02:41.075CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv	The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism
title	The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism
spellingShingle	The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism Sebastián, Carlos Sirt6 Cancer Metabolism
title_short	The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism
title_full	The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism
title_fullStr	The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism
title_full_unstemmed	The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism
title_sort	The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism
dc.creator.none.fl_str_mv	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
author	Sebastián, Carlos
author_facet	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
author_role	author
author2	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
author2_role	author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Sirt6 Cancer Metabolism
topic	Sirt6 Cancer Metabolism
purl_subject.fl_str_mv	https://purl.org/becyt/ford/3.3 https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv	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. Fil: Sebastián, Carlos. Harvard Medical School; Estados Unidos Fil: Zwaans, Bernardette M. M.. University of Michigan; Estados Unidos Fil: Silberman, Dafne Magali. Harvard Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Gymrek, Melissa. Massachusetts Institute of Technology; Estados Unidos Fil: Goren, Alon. Harvard Medical School; Estados Unidos. Massachusetts Institute of Technology; Estados Unidos Fil: Zhong, Lei. Harvard Medical School; Estados Unidos Fil: Ram, Oren. Harvard Medical School; Estados Unidos. Massachusetts Institute of Technology; Estados Unidos Fil: Truelove, Jessica. The Massachusetts General Hospital; Estados Unidos Fil: Guimaraes, Alexander R.. The Massachusetts General Hospital; Estados Unidos Fil: Toiber, Debra. Harvard Medical School; Estados Unidos Fil: Cosentino, Claudia. Harvard Medical School; Estados Unidos Fil: Greenson, Joel K.. University of Michigan; Estados Unidos Fil: MacDonald, Alasdair I.. University of Glasgow; Reino Unido Fil: McGlynn, Liane. University of Glasgow; Reino Unido Fil: Maxwell, Fraser. University of Glasgow; Reino Unido Fil: Edwards, Joanne. University of Glasgow; Reino Unido Fil: Giacosa, Sofía. Harvard Medical School; Estados Unidos Fil: Guccione, Ernesto. Institute of Molecular and Cell Biology; Singapur Fil: Weissleder, Ralph. The Massachusetts General Hospital; Estados Unidos Fil: Bernstein, Bradley E.. Harvard Medical School; Estados Unidos Fil: Regev, Aviv. Harvard Medical School; Estados Unidos Fil: Shiels, Paul G.. University of Glasgow; Reino Unido Fil: Lombard, David B.. University of Michigan; Estados Unidos Fil: Mostoslavsky, Raul. Harvard Medical School; Estados Unidos
description	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.
publishDate	2012
dc.date.none.fl_str_mv	2012-12
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/11336/17712 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 0092-8674
url	http://hdl.handle.net/11336/17712
identifier_str_mv	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 0092-8674
dc.language.none.fl_str_mv	eng
language	eng
dc.relation.none.fl_str_mv	info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0092867412013517 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2012.10.047
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv	openAccess
rights_invalid_str_mv	https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv	application/pdf application/pdf
dc.publisher.none.fl_str_mv	Elsevier
publisher.none.fl_str_mv	Elsevier
dc.source.none.fl_str_mv	reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str	CONICET Digital (CONICET)
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instname_str	Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv	CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv	dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism

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