ArticleCancer & metabolism2021
SIRT6 enhances oxidative phosphorylation in breast cancer and promotes mammary tumorigenesis in mice.
Article in Cancer & metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 44 citations in OpenAlex.
- Review
- Adipocyte-rich microenvironment promotes TNBC progression through SIRT6-associated ACSL5 dysregulation and lipid storage-associated phenotypes.Journal of experimental & clinical cancer research : CR · 2026Article
- Sirt6 promotes tumor growth and suppresses immune surveillance.Cancer cell international · 2026Article
- SIRT6 in Cancer: Mechanistic Insights into Its Dual Roles in Cancer Biology and Implications for Precision Therapeutic Development.Biomolecules · 2025Review
- Nutritional ketosis modulates the methylation of cancer-related genes in patients with obesity and in breast cancer cells.Journal of physiology and biochemistry · 2025Article
- Mechanisms of chemotherapy failure in refractory/relapsed acute myeloid leukemia: the role of cytarabine resistance and mitochondrial metabolism.Cell death & disease · 2025Article
- Increased Sirtuin 6 Activity in Tumor Cells Can Prompt CD4-Positive T-Cell Differentiation Into Regulatory T Cells and Impede Immune Surveillance in the Microenvironment.World journal of oncology · 2025Article
- Histone acetylation modulators in breast cancer.Breast cancer research : BCR · 2025Review
- Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development.Frontiers in immunology · 2025Review
- Apolipoproteins have a major role in cellular tumor dormancy in triple negative breast cancer: In-silico study.Scientific reports · 2024Article
- Post-translational modifications of pyruvate dehydrogenase complex in cardiovascular disease.iScience · 2024Review
- The evolving process of ferroptosis in thyroid cancer: Novel mechanisms and opportunities.Journal of cellular and molecular medicine · 2024Review
- NNMT/1-MNA Promote Cell-Cycle Progression of Breast Cancer by Targeting UBC12/Cullin-1-Mediated Degradation of P27 Proteins.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- SIRT6 promotes metastasis and relapse in HER2-positive breast cancer.Scientific reports · 2023Article
- Cyclic fasting bolsters cholesterol biosynthesis inhibitors' anticancer activity.Nature communications · 2023Article
- Effects of Deacetylase Inhibition on the Activation of the Antioxidant Response and Aerobic Metabolism in Cellular Models of Fanconi Anemia.Antioxidants (Basel, Switzerland) · 2023Article
- Determination and characterization of molecular heterogeneity and precision medicine strategies of patients with pancreatic cancer and pancreatic neuroendocrine tumor based on oxidative stress and mitochondrial dysfunction-related genes.Frontiers in endocrinology · 2023Article
- Exploration of prognostic genes and risk signature in breast cancer patients based on RNA binding proteins associated with ferroptosis.Frontiers in genetics · 2023Article
- PLX4032 resistance of patient-derived melanoma cells: crucial role of oxidative metabolism.Frontiers in oncology · 2023Article
- Breast Cancer with Increased Drug Resistance, Invasion Ability, and Cancer Stem Cell Properties through Metabolism Reprogramming.International journal of molecular sciences · 2022Article
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSirtuin 6 (SIRT6) is a NAD
methodsWe evaluated the effect of a heterozygous deletion of Sirt6 on tumor latency and survival of mouse mammary tumor virus (MMTV)-PyMT mice. The effect of SIRT6 silencing on human BC cell growth was assessed in MDA-MB-231 xenografts. We also analyzed the effect of Sirt6 heterozygous deletion, of SIRT6 silencing, and of the overexpression of either wild-type (WT) or catalytically inactive (H133Y) SIRT6 on BC cell pyruvate dehydrogenase (PDH) expression and activity and oxidative phosphorylation (OXPHOS), including respiratory complex activity, ATP/AMP ratio, AMPK activation, and intracellular calcium concentration.
resultsThe heterozygous Sirt6 deletion extended tumor latency and mouse survival in the MMTV-PyMT mouse BC model, while SIRT6 silencing slowed the growth of MDA-MB-231 BC cell xenografts. WT, but not catalytically inactive, SIRT6 enhanced PDH expression and activity, OXPHOS, and ATP/AMP ratio in MDA-MB-231 and MCF7 BC cells. Opposite effects were obtained by SIRT6 silencing, which also blunted the expression of genes encoding for respiratory chain proteins, such as UQCRFS1, COX5B, NDUFB8, and UQCRC2, and increased AMPK activation in BC cells. In addition, SIRT6 overexpression increased, while SIRT6 silencing reduced, intracellular calcium concentration in MDA-MB-231 cells. Consistent with these findings, the heterozygous Sirt6 deletion reduced the expression of OXPHOS-related genes, the activity of respiratory complexes, and the ATP/AMP ratio in tumors isolated from MMTV-PyMT mice.
conclusionsVia its enzymatic activity, SIRT6 enhances PDH expression and activity, OXPHOS, ATP/AMP ratio, and intracellular calcium concentration, while reducing AMPK activation, in BC cells. Thus, overall, SIRT6 inhibition appears as a viable strategy for preventing or treating BC.
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