ArticleThe Journal of biological chemistry2014
Mechanism of metformin-dependent inhibition of mammalian target of rapamycin (mTOR) and Ras activity in pancreatic cancer: role of specificity protein (Sp) transcription factors.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 3 of them syntheses that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
87 citing papers in PubMed, 3 syntheses or guidelines pooled it, 129 citations in OpenAlex.
- Effect of Metformin and Statin Use on Survival in Pancreatic Cancer Patients: a Systematic Literature Review and Meta-analysis.Current medicinal chemistry · 2018Pooled it
- Metformin therapy and risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients: A systematic review and meta-analysis.Oncotarget · 2017 · on this mapPooled it
- Effect of Metformin Use on Survival in Resectable Pancreatic Cancer: A Single-Institution Experience and Review of the Literature.PloS one · 2016Pooled it
- Trial
- Beyond diabetes mellitus: role of metformin in non-muscle-invasive bladder cancer.Singapore medical journal · 2022Trial
- Comparison of Metformin Combinations with Other Repurposed Drugs in the Treatment of Hamster Fibrosarcoma: A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Metformin in skin diseases: the role of gut microbiota and immune response.Pharmacological reports : PR · 2026Review
- Mapping the current research landscape of metformin in cancer based on bibliometric analysis.Discover oncology · 2025Article
- Diverse roles of stress-responsive RNP granules in oogenesis and infertility.Biology of reproduction · 2025Review
- In vitro Evaluation of Zinc Oxide-Metformin Folic Acid Nanocomposite as a Targeted Drug Delivery System for Cancer Therapy.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Metformin as a disease-modifying therapy in osteoarthritis: bridging metabolism and joint health.Frontiers in pharmacology · 2025Article
- Metformin in Chemoprevention of Lung Cancer: A Retrospective Population-Based Cohort Study in Lithuania.Medicina (Kaunas, Lithuania) · 2024Article
- Human Aging and Age-Related Diseases: From Underlying Mechanisms to Pro-Longevity Interventions.Aging and disease · 2024Review
- Metformin: A Dual-Role Player in Cancer Treatment and Prevention.International journal of molecular sciences · 2024Review
- Specificity Proteins (Sp) and Cancer.International journal of molecular sciences · 2023Review
- Action Mechanism of Metformin and Its Application in Hematological Malignancy Treatments: A Review.Biomolecules · 2023Review
- Metformin extends the chronological lifespan of fission yeast by altering energy metabolism and stress resistance capacity.FEMS yeast research · 2023Article
- Drugs against metabolic diseases as potential senotherapeutics for aging-related respiratory diseases.Frontiers in endocrinology · 2023Review
- Current trends and future prospects of drug repositioning in gastrointestinal oncology.Frontiers in pharmacology · 2023Review
- Molecular inhibition of RAS signalling to target ageing and age-related health.Disease models & mechanisms · 2022Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
The antidiabetic drug metformin exhibits both chemopreventive and chemotherapeutic activity for multiple cancers including pancreatic cancer; however, the underlying mechanism of action of metformin is unclear. A recent study showed that metformin down-regulated specificity protein (Sp) transcription factors (TFs) Sp1, Sp3, and Sp4 in pancreatic cancer cells and tumors, and this was accompanied by down-regulation of several pro-oncogenic Sp-regulated genes. Treatment with metformin or down-regulation of Sp TFs by RNAi also inhibits two major pro-oncogenic pathways in pancreatic cancer cells, namely mammalian target of rapamycin (mTOR) signaling and epidermal growth factor (EGFR)-dependent activation of Ras. Metformin and Sp knockdown by RNAi decreased expression of the insulin-like growth factor-1 receptor (IGF-1R), resulting in inhibition of mTOR signaling. Ras activity was also decreased by metformin and Sp knockdown of EGFR, another Sp-regulated gene. Thus, the antineoplastic activities of metformin in pancreatic cancer are due, in part, to down-regulation of Sp TFs and Sp-regulated IGF-1R and EGFR, which in turn results in inhibition of mTOR and Ras signaling, respectively.
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Registered trials
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.