ArticleApoptosis : an international journal on programmed cell death2022
The histone deacetylase SIRT6 promotes glycolysis through the HIF-1α/HK2 signaling axis and induces erlotinib resistance in non-small cell lung cancer.
Article in Apoptosis : an international journal on programmed cell death, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Research progress on lysine acetylation (Review).International journal of molecular medicine · 2026Review
- LPIN2 contributes to tyrosine kinase inhibitor resistance via activation of PI3K pathway.Translational lung cancer research · 2026Article
- Identifying PLAU as a shared pathogenic gene in type 2 diabetes and bladder urothelial carcinoma through integrated transcriptomic analysis and machine learning for diagnostic and therapeutic value.Clinical and experimental medicine · 2026Article
- Subtype-specific sirtuin expression signatures link mitochondrial-epigenetic networks to breast cancer survival.GeroScience · 2026Article
- Targeting Glycolytic Metabolism in Cancer Therapy: Current Approaches and Future Perspectives.Cells · 2026Review
- Hypoxia-Inducible Factor 1-α in Autoimmune Diseases-Insights from the Paradigm of Hashimoto's Thyroiditis: A Narrative Review.Medical sciences (Basel, Switzerland) · 2026Review
- EGFR-19del nuclear translocation increases HDAC7 expression inhibiting the Hippo pathway and exacerbating TKI resistance in lung adenocarcinoma.Theranostics · 2026Article
- Friend or foe? The role of SIRT6 on macrophage polarized to M2 subtype in acute kidney injury to chronic kidney disease.Renal failure · 2025Review
- SIRT6 in Cancer: Mechanistic Insights into Its Dual Roles in Cancer Biology and Implications for Precision Therapeutic Development.Biomolecules · 2025Review
- A Novel Microfluidic Platform for Circulating Tumor Cell Identification in Non-Small-Cell Lung Cancer.Micromachines · 2025Article
- Review
- Sirtuin family in lung adenocarcinoma.Discover oncology · 2025Review
- DNMBP-AS1/hsa-miR-30a-5p/PGC1α axis suppresses tumor progression of colorectal cancer by inhibiting PKM2-mediated Warburg effect and enhance anti-PD-1 therapy efficacy.Cell death discovery · 2025Article
- The Multifaceted Role of VIRMA, a Core Component of the Methyltransferase Complex, in Cancer and Cancer Therapy.Biomolecules · 2025Review
- Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development.Frontiers in immunology · 2025Review
- Unlocking the secrets of glucose metabolism reprogramming: the role in pulmonary diseases.Frontiers in pharmacology · 2025Review
- Sirtuins and tumor immunity: mechanistic insights, immunotherapy prospects, and therapeutic horizons.Frontiers in immunology · 2025Review
- Branched-chain amino acid transaminase 1 confers EGFR-TKI resistance through epigenetic glycolytic activation.Signal transduction and targeted therapy · 2024Article
- CCT6A facilitates lung adenocarcinoma progression and glycolysis via STAT1/HK2 axis.Journal of translational medicine · 2024Article
- The lactate metabolism and protein lactylation in epilepsy.Frontiers in cellular neuroscience · 2024Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Erlotinib is a first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Overcoming erlotinib resistance is crucial to improve the survival of advanced non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. It is also an important clinical problem that urgently needs a solution. In this study, we explored strategies to overcome erlotinib resistance from the perspective of energy metabolism. SIRT6 is a histone deacetylase. Here, we found that high expression of SIRT6 is associated with poor prognosis of lung adenocarcinoma, especially in EGFR-mutated NSCLC patients. The next cell experiment found that SIRT6 expression increased in erlotinib-resistant cells, and SIRT6 expression was negatively correlated with the sensitivity of NSCLC to erlotinib. Inhibition of SIRT6 promoted erlotinib-induced apoptosis in erlotinib-resistant cells, and glycolysis in drug-resistant cells was also inhibited. Functional studies have shown that SIRT6 increases glycolysis through the HIF-1α/HK2 signaling axis in drug-resistant cells and inhibits the sensitivity of NSCLC cells to erlotinib. In addition, the HIF-1α blocker PX478-2HCL attenuated the glycolysis and erlotinib resistance induced by SIRT6. More importantly, we confirmed the antitumor effect of SIRT6 inhibition combined with erlotinib in NSCLC-bearing mice. Our findings indicate that the cancer metabolic pathway regulated by SIRT6 may be a new target for attenuating NSCLC erlotinib resistance and has potential as a biomarker or therapeutic target to improve outcomes in NSCLC patients.
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