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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In the citing paper
“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
In the citing paper
“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
In the citing paper
“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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1 retracted
RETRACTED: Human SIRT6 Promotes DNA End Resection Through CtIP Deacetylation
Kaidi, A., Weinert, B. T., Choudhary, C., & Jackson, S. P. (2010) · Science · doi:10.1126/science.1192049 · Cited by 366
RetractedHallmarks of Cancer: The Next Generation
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BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
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TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,682
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
Barretina, J., Caponigro, G., Stransky, N., Venkatesan, K., Margolin, A. A., Kim, S., Wilson, C. J., Lehár, J., Kryukov, G. V., Sonkin, D., et al. (2012) · Nature · doi:10.1038/nature11003 · Cited by 7,950
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1 of the 65 references couldn’t be matched to a known paper.
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SIRT1 and other sirtuins in metabolism
Chang, H.-C., & Guarente, L. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.12.001 · Cited by 1,157
Histone Modifications and CancerPreprint
Audia, J. E., & Campbell, R. M. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a019521 · Cited by 1,060
Influence of Metabolism on Epigenetics and Disease
Kaelin, W. G., & McKnight, S. L. (2013) · Cell · doi:10.1016/j.cell.2013.03.004 · Cited by 920
Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence
Rajman, L., Chwalek, K., & Sinclair, D. A. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.011 · Cited by 865
Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds
Bonkowski, M. S., & Sinclair, D. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.93 · Cited by 834
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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