The DOI matches its Crossref record; 64 of the 65 references it cites were found in a registry or an index.
The Histone Deacetylase SIRT6 Is a Tumor Suppressor that Controls Cancer Metabolism
Open accessAbstract
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.
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“the genes encoding SIRT3 and SIRT6 are tumor suppressors”
From Influence of Metabolism on Epigenetics and Disease (2013) · cites this paper as Sebastián et al., 2012
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“the battery of SIRT6 target genes (Sebastián et al., 2012) has been reported to overlap significantly with genes codependent on the c-Myc oncoprotein and the SAGA/GCN5 histone acetylase complex”
From Influence of Metabolism on Epigenetics and Disease (2013) · cites this paper as Sebastián et al., 2012
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“SIRT6 is a pro-longevity factor that exerts tumor suppression by inhibiting the transcriptional output of HIF1 and MYC.229”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [229]
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Metadata
- Authors
- Sebastián, C., Zwaans, B. M. M., Silberman, D. M., Gymrek, M., Goren, A., Zhong, L., Ram, O., Truelove, J., Guimaraes, A. R., Toiber, D., Cosentino, C., Greenson, J. K., MacDonald, A. I., McGlynn, L., Maxwell, F., Edwards, J., Giacosa, S., Guccione, E., Weissleder, R., Bernstein, B. E., Regev, A., Shiels, P. G., Lombard, D. B., & Mostoslavsky, R.
- Affiliations
- Harvard University (US)
- University of Michigan (US)
- Harvard–MIT Division of Health Sciences and Technology (US)
- Broad Institute (US)
- Massachusetts General Hospital (US)
- University of Glasgow (GB)
- Institute of Molecular and Cell Biology (SG)
- Corresponding author
- Lombard, David B.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 151
- Issue
- 6
- Pages
- 1185-1199
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3526953
- OpenAlex
- W2138062757
- Cited by
- 660
- References
- 65
- Citations by year
- 2026: 26 · 2025: 23 · 2024: 27 · 2023: 36 · 2022: 51 · 2021: 52 · 2020: 52 · 2019: 47 · 2018: 53 · 2017: 53 · 2016: 63 · 2015: 59 · 2014: 54 · 2013: 58 · 2012: 4
- FWCI
- 27.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-nd)
- Elsevier eBooks
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (P30AG013283)
- National Human Genome Research Institute (P50HG006193)
- National Cancer Institute (R01CA175727)
- National Institute of General Medical Sciences (GM093072-01, GM101171, R01GM093072, R01GM101171)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK088190-01A1, R01DK088190)
- National Institute of Biomedical Imaging and Bioengineering (K08EB012859)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- SIRT6, histone deacetylase, tumor suppressor, cancer metabolism, aerobic glycolysis, Warburg effect, tumor growth, prognosis, conditional knockout
- MeSH terms
- Animals, Fibroblasts, Glycolysis, Humans, Mice, Nude, Neoplasm Transplantation, Neoplasms, Transcription, Genetic, Transplantation, Heterologous, Down-Regulation, Proto-Oncogene Proteins c-myc, Mice, SCID, Tumor Suppressor Proteins, Sirtuins, Cell Proliferation, Mice, Gene Knockout Techniques
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