ArticleInternational journal of molecular sciences2016
Metformin Inhibits TGF-β1-Induced Epithelial-to-Mesenchymal Transition via PKM2 Relative-mTOR/p70s6k Signaling Pathway in Cervical Carcinoma Cells.
Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- The Role of Cytokines in Epithelial-Mesenchymal Transition in Gynaecological Cancers: A Systematic Review.Cells · 2023Pooled it
- Epithelial-mesenchymal transition and its role in drug resistance of cervical cancer.Molecular biology reports · 2026Review
- Targeting Tumour Heterogeneity through sequential timing of anti-hallmark combination therapies -a hypothesis for implementation.Frontiers in immunology · 2026Review
- TGF-beta inhibitors in cancer therapy: a review of the TGF-beta signal transduction pathway and current developments.EXCLI journal · 2026Review
- Review
- Induction of CXCL8 by endoplasmic reticulum stress promotes migration and invasion of esophageal squamous cell carcinoma through activation of SMAD2/3.Molecular medicine reports · 2025Article
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Metformin in gynecological disorders: pathogenic insights and therapeutic implications.Frontiers in pharmacology · 2025Review
- Roles of gut microbiome-associated metabolites in pulmonary fibrosis by integrated analysis.NPJ biofilms and microbiomes · 2024Article
- Article
- Effect of Metformin on Sertoli Cell Fatty Acid Metabolism and Blood-Testis Barrier Formation.Biology · 2024Article
- The anti-inflammatory effect of metformin: The molecular targets.Genes to cells : devoted to molecular & cellular mechanisms · 2024Review
- Review
- Metformin and Cervical Cancer Risk in Patients with Newly Diagnosed Type 2 Diabetes: A Population-Based Study in Korea.Endocrinology and metabolism (Seoul, Korea) · 2022Article
- Targeting Energy Metabolism in Cancer Treatment.International journal of molecular sciences · 2022Review
- Tumor microenvironment in non-melanoma skin cancer resistance to photodynamic therapy.Frontiers in oncology · 2022Review
- Infection by High-Risk Human Papillomaviruses, Epithelial-to-Mesenchymal Transition and Squamous Pre-Malignant or Malignant Lesions of the Uterine Cervix: A Series of Chained Events?International journal of molecular sciences · 2021Review
- TGF-β links glycolysis and immunosuppression in glioblastoma.Histology and histopathology · 2021Review
- Tumor pyruvate kinase M2 modulators: a comprehensive account of activators and inhibitors as anticancer agents.RSC medicinal chemistry · 2021Review
- Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEpithelial-to-mesenchymal transition (EMT) plays a prominent role in tumorigenesis. Metformin exerts antitumorigenic effects in various cancers. This study investigated the mechanisms of metformin in TGF-β1-induced Epithelial-to-mesenchymal transition (EMT) in cervical carcinoma cells.
methodscells were cultured with 10 ng/mL TGF-β1 to induce EMT and treated with or without metformin. Cell viability was evaluated by CCK-8 (Cell Counting Kit 8, CCK-8) assay; apoptosis were analyzed by flow cytometry; cell migration was evaluated by wound-healing assay. Western blotting was performed to detect E-cadherin, vimentin, signal transducer and activator of transcription 3 (STAT3), snail family transcriptional repressor 2 (SNAIL2), phosphorylation of p70s6k (p-p70s6k) and -Pyruvate kinase M2 (PKM2) Results: TGF-β1 promoted proliferation and migration, and it attenuated apoptosis compared with cells treated with metformin with or without TGF-β1 in cervical carcinoma cells. Moreover, metformin partially abolished TGF-β1-induced EMT cell proliferation and reversed TGF-β1-induced EMT. In addition, the anti-EMT effects of metformin could be partially in accord with rapamycin, a specific mTOR inhibitor. Metformin decreased the p-p70s6k expression and the blockade of mTOR/p70s6k signaling decreased PKM2 expression.
conclusionMetformin abolishes TGF-β1-induced EMT in cervical carcinoma cells by inhibiting mTOR/p70s6k signaling to down-regulate PKM2 expression. Our study provides a novel mechanistic insight into the anti-tumor effects of metformin.
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Registered trials
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