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Updated: May 16, 2026
14:32
Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates
Published on: February 27, 2016
The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism
Carlos Sebastián1, Bernadette M M Zwaans, Dafne M Silberman
1The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Cell
|December 11, 2012
Summary
SIRT6 acts as a tumor suppressor by regulating cancer cell metabolism. Loss of SIRT6 promotes tumor growth and aggressiveness, highlighting its critical role in cancer development and progression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metabolism
Background:
- Cellular metabolism reprogramming is crucial for tumor development (Warburg effect).
- Molecular mechanisms controlling metabolic shifts in cancer remain largely unknown.
- SIRT6's role in cancer metabolism has not been previously elucidated.
Purpose of the Study:
- To identify molecular regulators of cancer cell metabolism.
- To investigate the function of SIRT6 as a tumor suppressor.
- To determine SIRT6's role in cancer establishment and maintenance.
Main Methods:
- Utilized a conditional SIRT6 allele for in vivo studies.
- Assessed tumor formation, growth, and aggressiveness upon SIRT6 deletion.
- Investigated SIRT6's regulation of aerobic glycolysis and MYC transcriptional activity.
- Analyzed SIRT6 expression in human cancers and correlated with patient prognosis.
Main Results:
- SIRT6 deletion in vivo significantly increased tumor number, size, and aggressiveness.
- SIRT6-deficient cells exhibited enhanced glycolysis and tumor growth.
- SIRT6 was identified as a repressor of MYC transcriptional activity, regulating ribosome metabolism.
- Downregulation of SIRT6 in human cancers correlated with poor prognosis and reduced tumor-free survival.
Conclusions:
- SIRT6 is a critical tumor suppressor that suppresses cancer metabolism.
- Loss of SIRT6 promotes both the establishment and maintenance of cancer.
- SIRT6 expression levels serve as a prognostic marker for several human cancers.
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