ArticleJournal of experimental & clinical cancer research : CR2018
Upregulation of lactate-inducible snail protein suppresses oncogene-mediated senescence through p16
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 118 citations in OpenAlex.
- Glucose-induced histone lactylation confers metformin resistance in colorectal cancer stem cells.Nature communications · 2026Article
- Bidirectional Feedback Between Metabolic Reprogramming and Epithelial-Mesenchymal Transition: From Mechanisms to Therapeutic Interventions.Molecules (Basel, Switzerland) · 2026Review
- AFP Stimulates Glucose Metabolic Reprogramming Contributing to Hepatocellular Carcinoma Resist Sorafenib Through Activating PI3K/AKT Signalling Pathway.Journal of cellular and molecular medicine · 2026Article
- Effect of TGFβ-ITGB6 feedback loop on liver metastasis in SMAD4 wild-type pancreatic cancer.Chinese medical journal · 2026Article
- Lactate and lactylation: metabolic architects of tumor progression and metastasis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- BMAL1 Drives Cisplatin Resistance in Non-Small Cell Lung Cancer Via Lactate-MRP1 Signaling Pathway.Thoracic cancer · 2026Article
- [Advances in Lactate Metabolic Reprogramming in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Lactic Acid in Tumour Biology.Metabolites · 2026Review
- Investigating the Mechanistic Link Between Lactate-Induced Histone Lactylation and Cellular Senescence in Osteoarthritis Chondrocytes: Implications for Therapy.International journal of biological sciences · 2026Article
- The lactylation axis: bridging metabolic reprogramming and immunosuppression in the tumor microenvironment.Frontiers in immunology · 2026Review
- Lactylation in cancer biology: Unlocking new avenues for research and therapy.Cancer communications (London, England) · 2025Review
- Lactate and Lactylation in Respiratory Diseases: from Molecular Mechanisms to Targeted Strategies.Lung · 2025Review
- Downregulation of miR-27a-3p Modulates TGF-β Signaling and Dysregulates Metabolism in Glioblastoma.International journal of molecular sciences · 2025Article
- PGC1A Restores Mitochondrial Health to Attenuate EMT During Lens Epithelial Fibrosis via Regulating TFAM.Investigative ophthalmology & visual science · 2025Article
- WTAP Mediated m6A Modification Stabilizes PDIA3P1 and Promotes Tumor Progression Driven by Histone Lactylation in Esophageal Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exploring the interplay between LDHA and ABCC1 in breast cancer using computational approach.Discover oncology · 2025Article
- Article
- Carnitine palmitoyltransferase 1C promotes EMT-associated cisplatin resistance in non-small cell lung cancer cells.Cancer biology & medicine · 2025Article
- Organotropic metastasis in colorectal cancer: integrating molecular pathways with therapeutic opportunities.Frontiers in immunology · 2025Review
- The role of glycolysis in tumorigenesis: From biological aspects to therapeutic opportunities.Neoplasia (New York, N.Y.) · 2024Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe preferential use of aerobic glycolysis by tumor cells lead to high accumulation of lactate in tumor microenvironment. Clinical evidence has linked elevated lactate concentration with cancer outcomes. However, the role and molecular mechanisms of lactate in cellular senescence and tumor progression remain elusive.
methodsThe function of Snail in lactate-induced EMT in lung cancer cells was explored by wound healing assay and cell invasion assay. The qRT-PCR and dual luciferase reporter assay were performed to investigate how lactate regulates Snail expression. The level of TGF-β1 in culture supernatant of cells was measured by ELISA for its correlation with extracellular levels of lactate. Ras activity assay and SA-β-gal activity assay were established to determine the effect of lactate on oncogene-induced senescence in human lung epithelial cells. ChIP assays were conducted to determine the binding of snail to p16
resultsIn this study, we showed the invasive and migratory potential of lung cancer cells was significantly enhanced by lactate and was directly linked to snail activity. We also demonstrated that extracellular acidification itself is a direct cause of the increased snail expression and physiologically coupled to LDHA-dependent conversion of pyruvate to lactate. Mechanistically, lactate exerts its central function in induction of snail and EMT by directly remodeling ECM and releasing activated TGF-β1. We also demonstrated that Snail help premalignant cells to escape the oncogene-induced senescence by directly targeting and inhibiting p16
conclusionsOur study extends the understanding of EMT in tumorigenesis by uncovering the role of snail in cellular senescence. This study also reveals lactate may be a potent tumor-promoting factor and provides the basis for the development of lactate-targeted therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.