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  11. The Histone Deacetylase Sirt6 Is A Tumor Suppressor That Controls Cancer Metabolism.

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

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View abstract on PubMed

Summary
This summary is machine-generated.

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.

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Related Concept Videos

  • 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.