ArticleInternational journal of cancer2012
Association of activated c-Met with NRAS-mutated human melanomas.
Article in International journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 35 citations in OpenAlex.
- Development of Personalized Strategies for Precisely Battling Malignant Melanoma.International journal of molecular sciences · 2024Review
- SEMAPHORINS and their receptors: focus on the crosstalk between melanoma and hypoxia.Journal of experimental & clinical cancer research : CR · 2021Review
- RTK Inhibitors in Melanoma: From Bench to Bedside.Cancers · 2021Review
- HGF/c-MET Signaling in Melanocytes and Melanoma.International journal of molecular sciences · 2018Review
- Role of the HGF/c-MET tyrosine kinase inhibitors in metastasic melanoma.Molecular cancer · 2018Review
- MicroRNA-Directed Cancer Therapies: Implications in Melanoma Intervention.The Journal of pharmacology and experimental therapeutics · 2018Review
- Resistance mechanisms to genetic suppression of mutant NRAS in melanoma.Melanoma research · 2017Article
- Role Played by Signalling Pathways in Overcoming BRAF Inhibitor Resistance in Melanoma.International journal of molecular sciences · 2017Review
- Article
- Article
- Hypoxia-Driven Mechanism of Vemurafenib Resistance in Melanoma.Molecular cancer therapeutics · 2016Article
- Review
- Other targeted drugs in melanoma.Annals of translational medicine · 2015Review
- Mutational status of naevus-associated melanomas.The British journal of dermatology · 2015Article
- Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma.Cancers · 2015Article
- Article
- Quercetin inhibits HGF/c-Met signaling and HGF-stimulated melanoma cell migration and invasion.Molecular cancer · 2015Article
- Phase 1 trial of tivantinib in combination with sorafenib in adult patients with advanced solid tumors.Investigational new drugs · 2015Article
- Phosphoproteomic analysis of basal and therapy-induced adaptive signaling networks in BRAF and NRAS mutant melanoma.Proteomics · 2015Article
- The role of microRNAs and long non-coding RNAs in the pathology, diagnosis, and management of melanoma.Archives of biochemistry and biophysics · 2014Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Cutaneous melanomas can be divided into three mutually exclusive genetic subsets: tumors with mutated BRAF, tumors with mutated NRAS and tumors wild type at both loci (wt/wt). Targeted therapy for melanoma has been advancing with agents directed to mutated BRAF, accounting for 50% of melanoma patients. The c-Met pathway is known to play a role in melanoma tumorigenesis and preliminary data from our laboratory suggested that this pathway is preferentially activated in NRAS-mutated tumors. The objective of this study was to test the hypothesis that melanomas carrying the mutated NRAS genotype are uniquely sensitively to c-Met inhibition, thus providing rationale for therapeutic targeting of c-Met in this patient cohort. Using primary human melanomas with known BRAF/NRAS genotypes, we observed greater immunostaining for phosphorylated (activated) c-Met in NRAS-mutated and wt/wt tumors, compared to BRAF-mutated tumors. NRAS-mutated and wt/wt cell lines also demonstrated more robust c-Met activation in response to hepatocyte growth factor (HGF). Knock-down of mutated N-Ras, but not wild type N-Ras, by RNA interference resulted in decreased c-Met phosphorylation. Compared to BRAF mutants, NRAS-mutated melanoma cells were more sensitive to pharmacologic c-Met inhibition in terms of c-Met activation, Akt phosphorylation, tumor cell proliferation, migration and apoptosis. This enhanced sensitivity was observed in wt/wt cells as well, but was a less consistent finding. On the basis of these experimental results, we propose that c-Met inhibition may be a useful therapeutic strategy for melanomas with NRAS mutations, as well as some tumors with a wt/wt genotype.
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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.