ArticleCancer discovery2012
Metformin accelerates the growth of BRAF V600E-driven melanoma by upregulating VEGF-A.
Article in Cancer discovery, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.
- Enhancing the Efficacy of Metformin in Neoadjuvant Therapy for Breast Cancer: A Meta-Analysis Based on Randomized Clinical Trials.Cancer control : journal of the Moffitt Cancer CenterPooled it
- Trial
- Sorafenib synergizes with metformin in NSCLC through AMPK pathway activation.International journal of cancer · 2015Trial
- Metformin and its Nanoformulations in Cancer Prevention and Therapy.Current pharmaceutical design · 2025Review
- Treatment resistance to melanoma therapeutics on a single cell level.Scientific reports · 2024Article
- Therapeutic implications of the metabolic changes associated with BRAF inhibition in melanoma.Cancer treatment reviews · 2024Review
- Metabolic Profiling to Assess Response to Targeted and Immune Therapy in Melanoma.International journal of molecular sciences · 2024Review
- A Mammalian Conserved Circular RNA CircLARP1B Regulates Hepatocellular Carcinoma Metastasis and Lipid Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- WNT5A-ROR2 axis mediates VEGF dependence of BRAF mutant melanoma.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- NDUFS3 knockout cancer cells and molecular docking reveal specificity and mode of action of anti-cancer respiratory complex I inhibitors.Open biology · 2022Article
- Antidiabetics, Anthelmintics, Statins, and Beta-Blockers as Co-Adjuvant Drugs in Cancer Therapy.Medicina (Kaunas, Lithuania) · 2022Review
- Diabetes mellitus in relation to colorectal tumor molecular subtypes: A pooled analysis of more than 9000 cases.International journal of cancer · 2022Article
- Metformin: A promising drug for human cancers.Oncology letters · 2022Review
- Biological aspects in controlling angiogenesis: current progress.Cellular and molecular life sciences : CMLS · 2022Review
- [The role of metformin in the treatment of dermatological diseases: A narrative review].Atencion primaria · 2022Review
- Metformin Intervention-A Panacea for Cancer Treatment?Cancers · 2022Review
- PBLD inhibits angiogenesis via impeding VEGF/VEGFR2-mediated microenvironmental cross-talk between HCC cells and endothelial cells.Oncogene · 2022Article
- Article
- Apoptosis Pathways Triggered by a Potent Antiproliferative Hybrid Chalcone on Human Melanoma Cells.International journal of molecular sciences · 2021Article
- Metformin inhibits gastric cancer cell proliferation by regulation of a novel Loc100506691-CHAC1 axis.Molecular therapy oncolytics · 2021Article
15 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
4 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledThe antidiabetic drug metformin has antitumor activity in a variety of cancers because it blocks cell growth by inhibiting TORC1. Here, we show that melanoma cells that are driven by oncogenic BRAF are resistant to the growth-inhibitory effects of metformin because RSK sustains TORC1 activity even when AMP-activated protein kinase (AMPK) is activated. We further show that AMPK targets the dual-specificity protein phosphatase DUSP6 for degradation and this increases ERK activity, which then upregulates the VEGF-A protein. Critically, this drives angiogenesis and accelerates the growth of BRAF-driven tumors in mice. Unexpectedly, however, when VEGF signaling is inhibited, instead of accelerating tumor growth, metformin inhibits tumor growth. Thus, we show that BRAF-driven melanoma cells are resistant to the antigrowth effects of AMPK and that AMPK mediates cell-autonomous and cell-nonautonomous effects that accelerate the growth of these cells in vivo. SIGNIFICANCE: Metformin inhibits the growth of most tumor cells, but BRAF-mutant melanoma cells are resistant to metformin in vitro, and metformin accelerates their growth in vivo. Unexpectedly, VEGF inhibitors and metformin synergize to suppress the growth of BRAF-mutant tumors, revealing a combination of drugs that may be effective in these patients.
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What OpenQuestion holds
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.