ArticleNature2014
Copper is required for oncogenic BRAF signalling and tumorigenesis.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 329 papers, 4 of them syntheses that pooled it.
What it found
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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
329 citing papers in PubMed, 4 syntheses or guidelines pooled it, 585 citations in OpenAlex.
- Cuproptosis as a therapeutic target in cancer: a Systematic Review and bibliometric analysis of the research landscape.Frontiers in oncology · 2025Pooled it
- Revolutionizing breast cancer treatment: Harnessing the related mechanisms and drugs for regulated cell death (Review).International journal of oncology · 2024Pooled it
- Risk mapping of lung cancer: a comprehensive appraisal of published meta-analyses incorporating Mendelian randomization studies.Journal of cancer research and clinical oncology · 2023Pooled it
- A Global Perspective of Correlation Between Maternal Copper Levels and Preeclampsia in the 21st Century: A Systematic Review and Meta-Analysis.Frontiers in public health · 2022Pooled it
- A Phase 1/2 Study of Disulfiram and Copper With Concurrent Radiation Therapy and Temozolomide for Patients With Newly Diagnosed Glioblastoma.International journal of radiation oncology, biology, physics · 2024Trial
- Systemic Copper Chelation Reduces Collagen Deposition and Preserves Secretory Function in Irradiated Mouse Salivary Glands.Advances in radiation oncology · 2026Article
- Structure-activity relationship of Cu(II) and Pd(II) thiosemicarbazone complexes with anticancer and antibacterial properties.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Research progress of pancreatic cancer based on ferroptosis-cuproptosis interaction (Review).Oncology letters · 2026Review
- Folic acid polyglutamylation triggers MAP2K5 signaling to induce adipocyte lipid catabolism.bioRxiv : the preprint server for biology · 2026Article
- Copper, cuproptosis, and cancer: biology concepts of a novel cell death.Apoptosis : an international journal on programmed cell death · 2026Review
- Balancing cellular copper levels via the post-translational regulation of copper transport.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Subtype-Specific Alterations in Copper Trafficking Associated with KRAS Mutations in Isogenic Colorectal Cancer Cell Lines.Biological trace element research · 2026Article
- Engineering cuproptosis with nanomedicine: Design, combination therapy, and translation in cancer.Materials today. Bio · 2026Review
- Copper depletion boosts CNS leukemia therapy by inhibiting nucleotide synthesis through impairment of mitochondrial complex IV activity.Nature cancer · 2026Article
- Copper homeostasis and cuproptosis rewire the tumor microenvironment: mechanisms, immune modulation, and therapeutic opportunities.Journal of hematology & oncology · 2026Review
- ATP7A-mediated copper ion efflux reprogrammes tumour immunity and promotes cisplatin resistance in cervical cancer.Cell death & disease · 2026Article
- Copper homeostasis and cuproptosis in cancer: mitochondrial metabolic dependency and nanomedicine-based therapeutic strategies.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- An entropy-driven, selective copper-sequestering coordination framework for gut-restricted intervention of Wilson's disease.Materials today. Bio · 2026Article
- Tumor CTR1 Expression and Systemic Copper Dynamics Converge on a Copper Axis in High-Grade Triple-Negative Breast Cancer.Cancer research communications · 2026Article
269 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The BRAF kinase is mutated, typically Val 600→Glu (V600E), to induce an active oncogenic state in a large fraction of melanomas, thyroid cancers, hairy cell leukaemias and, to a smaller extent, a wide spectrum of other cancers. BRAF(V600E) phosphorylates and activates the MEK1 and MEK2 kinases, which in turn phosphorylate and activate the ERK1 and ERK2 kinases, stimulating the mitogen-activated protein kinase (MAPK) pathway to promote cancer. Targeting MEK1/2 is proving to be an important therapeutic strategy, given that a MEK1/2 inhibitor provides a survival advantage in metastatic melanoma, an effect that is increased when administered together with a BRAF(V600E) inhibitor. We previously found that copper (Cu) influx enhances MEK1 phosphorylation of ERK1/2 through a Cu-MEK1 interaction. Here we show decreasing the levels of CTR1 (Cu transporter 1), or mutations in MEK1 that disrupt Cu binding, decreased BRAF(V600E)-driven signalling and tumorigenesis in mice and human cell settings. Conversely, a MEK1-MEK5 chimaera that phosphorylated ERK1/2 independently of Cu or an active ERK2 restored the tumour growth of murine cells lacking Ctr1. Cu chelators used in the treatment of Wilson disease decreased tumour growth of human or murine cells transformed by BRAF(V600E) or engineered to be resistant to BRAF inhibition. Taken together, these results suggest that Cu-chelation therapy could be repurposed to treat cancers containing the BRAF(V600E) mutation.
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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.