-transparent.png){kind=logo}
The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. 2012
Carlos Sebastián, and
Bernadette M M Zwaans, and
Dafne M Silberman, and
Melissa Gymrek, and
Alon Goren, and
Lei Zhong, and
Oren Ram, and
Jessica Truelove, and
Alexander R Guimaraes, and
Debra Toiber, and
Claudia Cosentino, and
Joel K Greenson, and
Alasdair I MacDonald, and
Liane McGlynn, and
Fraser Maxwell, and
Joanne Edwards, and
Sofia Giacosa, and
Ernesto Guccione, and
Ralph Weissleder, and
Bradley E Bernstein, and
Aviv Regev, and
Paul G Shiels, and
David B Lombard, and
Raul Mostoslavsky
The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
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.
Related Publications
Carlos Sebastián, and
Bernadette M M Zwaans, and
Dafne M Silberman, and
Melissa Gymrek, and
Alon Goren, and
Lei Zhong, and
Oren Ram, and
Jessica Truelove, and
Alexander R Guimaraes, and
Debra Toiber, and
Claudia Cosentino, and
Joel K Greenson, and
Alasdair I MacDonald, and
Liane McGlynn, and
Fraser Maxwell, and
Joanne Edwards, and
Sofia Giacosa, and
Ernesto Guccione, and
Ralph Weissleder, and
Bradley E Bernstein, and
Aviv Regev, and
Paul G Shiels, and
David B Lombard, and
Raul Mostoslavsky
March 2008,
Nature,
Carlos Sebastián, and
Bernadette M M Zwaans, and
Dafne M Silberman, and
Melissa Gymrek, and
Alon Goren, and
Lei Zhong, and
Oren Ram, and
Jessica Truelove, and
Alexander R Guimaraes, and
Debra Toiber, and
Claudia Cosentino, and
Joel K Greenson, and
Alasdair I MacDonald, and
Liane McGlynn, and
Fraser Maxwell, and
Joanne Edwards, and
Sofia Giacosa, and
Ernesto Guccione, and
Ralph Weissleder, and
Bradley E Bernstein, and
Aviv Regev, and
Paul G Shiels, and
David B Lombard, and
Raul Mostoslavsky
January 2013,
Current topics in medicinal chemistry,
Carlos Sebastián, and
Bernadette M M Zwaans, and
Dafne M Silberman, and
Melissa Gymrek, and
Alon Goren, and
Lei Zhong, and
Oren Ram, and
Jessica Truelove, and
Alexander R Guimaraes, and
Debra Toiber, and
Claudia Cosentino, and
Joel K Greenson, and
Alasdair I MacDonald, and
Liane McGlynn, and
Fraser Maxwell, and
Joanne Edwards, and
Sofia Giacosa, and
Ernesto Guccione, and
Ralph Weissleder, and
Bradley E Bernstein, and
Aviv Regev, and
Paul G Shiels, and
David B Lombard, and
Raul Mostoslavsky
March 2017,
Cell reports,
Carlos Sebastián, and
Bernadette M M Zwaans, and
Dafne M Silberman, and
Melissa Gymrek, and
Alon Goren, and
Lei Zhong, and
Oren Ram, and
Jessica Truelove, and
Alexander R Guimaraes, and
Debra Toiber, and
Claudia Cosentino, and
Joel K Greenson, and
Alasdair I MacDonald, and
Liane McGlynn, and
Fraser Maxwell, and
Joanne Edwards, and
Sofia Giacosa, and
Ernesto Guccione, and
Ralph Weissleder, and
Bradley E Bernstein, and
Aviv Regev, and
Paul G Shiels, and
David B Lombard, and
Raul Mostoslavsky
December 2011,
Cell death and differentiation,
Carlos Sebastián, and
Bernadette M M Zwaans, and
Dafne M Silberman, and
Melissa Gymrek, and
Alon Goren, and
Lei Zhong, and
Oren Ram, and
Jessica Truelove, and
Alexander R Guimaraes, and
Debra Toiber, and
Claudia Cosentino, and
Joel K Greenson, and
Alasdair I MacDonald, and
Liane McGlynn, and
Fraser Maxwell, and
Joanne Edwards, and
Sofia Giacosa, and
Ernesto Guccione, and
Ralph Weissleder, and
Bradley E Bernstein, and
Aviv Regev, and
Paul G Shiels, and
David B Lombard, and
Raul Mostoslavsky
January 2015,
American journal of cancer research,
Carlos Sebastián, and
Bernadette M M Zwaans, and
Dafne M Silberman, and
Melissa Gymrek, and
Alon Goren, and
Lei Zhong, and
Oren Ram, and
Jessica Truelove, and
Alexander R Guimaraes, and
Debra Toiber, and
Claudia Cosentino, and
Joel K Greenson, and
Alasdair I MacDonald, and
Liane McGlynn, and
Fraser Maxwell, and
Joanne Edwards, and
Sofia Giacosa, and
Ernesto Guccione, and
Ralph Weissleder, and
Bradley E Bernstein, and
Aviv Regev, and
Paul G Shiels, and
David B Lombard, and
Raul Mostoslavsky
January 2010,
Cell,
Carlos Sebastián, and
Bernadette M M Zwaans, and
Dafne M Silberman, and
Melissa Gymrek, and
Alon Goren, and
Lei Zhong, and
Oren Ram, and
Jessica Truelove, and
Alexander R Guimaraes, and
Debra Toiber, and
Claudia Cosentino, and
Joel K Greenson, and
Alasdair I MacDonald, and
Liane McGlynn, and
Fraser Maxwell, and
Joanne Edwards, and
Sofia Giacosa, and
Ernesto Guccione, and
Ralph Weissleder, and
Bradley E Bernstein, and
Aviv Regev, and
Paul G Shiels, and
David B Lombard, and
Raul Mostoslavsky
May 2015,
Nature cell biology,
Carlos Sebastián, and
Bernadette M M Zwaans, and
Dafne M Silberman, and
Melissa Gymrek, and
Alon Goren, and
Lei Zhong, and
Oren Ram, and
Jessica Truelove, and
Alexander R Guimaraes, and
Debra Toiber, and
Claudia Cosentino, and
Joel K Greenson, and
Alasdair I MacDonald, and
Liane McGlynn, and
Fraser Maxwell, and
Joanne Edwards, and
Sofia Giacosa, and
Ernesto Guccione, and
Ralph Weissleder, and
Bradley E Bernstein, and
Aviv Regev, and
Paul G Shiels, and
David B Lombard, and
Raul Mostoslavsky
May 2009,
Journal of medicinal chemistry,
Carlos Sebastián, and
Bernadette M M Zwaans, and
Dafne M Silberman, and
Melissa Gymrek, and
Alon Goren, and
Lei Zhong, and
Oren Ram, and
Jessica Truelove, and
Alexander R Guimaraes, and
Debra Toiber, and
Claudia Cosentino, and
Joel K Greenson, and
Alasdair I MacDonald, and
Liane McGlynn, and
Fraser Maxwell, and
Joanne Edwards, and
Sofia Giacosa, and
Ernesto Guccione, and
Ralph Weissleder, and
Bradley E Bernstein, and
Aviv Regev, and
Paul G Shiels, and
David B Lombard, and
Raul Mostoslavsky
March 2011,
Science (New York, N.Y.),
Carlos Sebastián, and
Bernadette M M Zwaans, and
Dafne M Silberman, and
Melissa Gymrek, and
Alon Goren, and
Lei Zhong, and
Oren Ram, and
Jessica Truelove, and
Alexander R Guimaraes, and
Debra Toiber, and
Claudia Cosentino, and
Joel K Greenson, and
Alasdair I MacDonald, and
Liane McGlynn, and
Fraser Maxwell, and
Joanne Edwards, and
Sofia Giacosa, and
Ernesto Guccione, and
Ralph Weissleder, and
Bradley E Bernstein, and
Aviv Regev, and
Paul G Shiels, and
David B Lombard, and
Raul Mostoslavsky
September 2002,
Nucleic acids research,
