ArticleScientific reports2023
SIRT6 promotes metastasis and relapse in HER2-positive breast cancer.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Conserved Transcriptomic Signatures of Sirt6 Activity: A Cross-Species RNA-seq Meta-analysis.bioRxiv : the preprint server for biology · 2026Article
- Squalene attenuates doxorubicin resistance in hepatocellular carcinoma by targeting SIRT6 to inhibit ERK1 deacetylation.Molecular and cellular biochemistry · 2026Article
- Mapping Non-Coding Epimutations in Breast Cancer: Advancing Epigenetics Towards Precision Medicine.Sub-cellular biochemistry · 2026Review
- Sirtuins in Women's Health.Pharmaceuticals (Basel, Switzerland) · 2025Review
- SIRT6 in Cancer: Mechanistic Insights into Its Dual Roles in Cancer Biology and Implications for Precision Therapeutic Development.Biomolecules · 2025Review
- Structural and enzymatic plasticity of SIRT6 deacylase activity.The Journal of biological chemistry · 2025Article
- Nutritional ketosis modulates the methylation of cancer-related genes in patients with obesity and in breast cancer cells.Journal of physiology and biochemistry · 2025Article
- Histone acetylation modulators in breast cancer.Breast cancer research : BCR · 2025Review
- Review
- SIRT6 deficiency impairs the deacetylation and ubiquitination of UHRF1 to strengthen glycolysis and lactate secretion in bladder cancer.Cell & bioscience · 2024Article
- Sirtuins as Key Regulators in Pancreatic Cancer: Insights into Signaling Mechanisms and Therapeutic Implications.Cancers · 2024Review
- A Novel Prognostic Model of Hepatocellular Carcinoma per Two NAD+ Metabolic Synthesis-Associated Genes.International journal of molecular sciences · 2024Article
- SIRT6 Inhibits Anoikis of Colorectal Cancer Cells by Down-Regulating NDRG1.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The histone deacetylase sirtuin 6 (SIRT6) has been endowed with anti-cancer capabilities in many tumor types. Here, we investigate the impact of SIRT6-overexpression (SIRT6-OE) in Delta16HER2 mice, which are a bona fide model of HER2-positive breast cancer. After an initial delay in the tumor onset, SIRT6-OE induces a more aggressive phenotype of Delta16HER2 tumors promoting the formation of higher number of tumor foci and metastases than controls. This phenotype of SIRT6-OE tumors is associated with cancer stem cell (CSC)-like features and tumor dormancy, and low senescence and oxidative DNA damage. Accordingly, a sub-set of HER2-positive breast cancer patients with concurrent SIRT6-OE has a significant poorer relapse-free survival (RFS) probability than patients with low expression of SIRT6. ChIP-seq, RNA-seq and RT-PCR experiments indicate that SIRT6-OE represses the expression of the T-box transcription factor 3 (Tbx3) by deacetylation of H3K9ac. Accordingly, loss-of-function mutations of TBX3 or low TBX3 expression levels are predictive of poor prognosis in HER2-positive breast cancer patients. Our work indicates that high levels of SIRT6 are indicative of poor prognosis and high risk of metastasis in HER2-positive breast cancer and suggests further investigation of TBX3 as a downstream target of SIRT6 and co-marker of poor-prognosis. Our results point to a breast cancer subtype-specific effect of SIRT6 and warrant future studies dissecting the mechanisms of SIRT6 regulation in different breast cancer subtypes.
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