Tier 3 — preclinical

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

Carlos Sebastián, Bernadette M M Zwaans, Dafne M Silberman, Melissa Gymrek, Alon Goren, Lei Zhong, Oren Ram, Jessica Truelove, Alexander R Guimaraes, Debra Toiber, Claudia Cosentino, Joel K Greenson, Alasdair I MacDonald, Liane McGlynn, Fraser Maxwell, Joanne Edwards, Sofia Giacosa, Ernesto Guccione, Ralph Weissleder, Bradley E Bernstein, Aviv Regev, Paul G Shiels, David B Lombard, Raul Mostoslavsky
Cell 2012 151(6):1185-1199

Bibliography

PubMed
PMID 23217706
PubMed Central
PMC3526953
DOI
10.1016/j.cell.2012.10.047
Funding
Supported by NIH grants including GM093072-01 and GM101171, the Sidney Kimmel Cancer Research Foundation, O'Connor Research Fund, Nathan Shock Center (AG013283), Pardee Foundation, and fellowship support.
Competing interests
No competing-interest statement was identified in the accessible full-text record.

Study snapshot

DesignMechanistic cancer-metabolism study using conditional SIRT6 loss, transformed cells, mouse tumor models and human tumor-expression analyses.
ModelCultured cells, conditional SIRT6 mouse models and human cancer tissue/expression datasets.
SampleMultiple preclinical and human-tissue cohorts; sample sizes vary by experiment.
InterventionGenetic SIRT6 deletion and metabolic pathway interrogation.
DurationExperiment-dependent.
EndpointsAerobic glycolysis; tumor formation and growth; MYC transcriptional activity; human tumor SIRT6 expression; tumor-free survival associations

What the study showed, in plain terms

This influential paper identified SIRT6 as a tumor suppressor in several experimental settings. Removing SIRT6 increased glycolysis and tumor growth, while human tumor datasets showed SIRT6 downregulation in several cancers.

Key findings

SIRT6 loss promoted a Warburg-like metabolic program and tumorigenesis, with HIF-1alpha and MYC-related mechanisms contributing to the phenotype.

What this study can and cannot tell us

Cancer biology is context-dependent. These findings do not mean that increasing SIRT6 is universally anti-cancer; later work reports settings in which SIRT6 activation can support tumor growth or immune evasion.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability