ArticleEBioMedicine2019
EGFR/uPAR interaction as druggable target to overcome vemurafenib acquired resistance in melanoma cells.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 43 citations in OpenAlex.
- The role of miR-335-5p in the redifferentiation of BRAF p.V600E thyroid cancers.Molecular oncology · 2026Article
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- Unraveling vascular mechanisms in melanoma: roles of angiogenesis and vasculogenic mimicry in tumor progression and therapeutic resistance.Cancer biology & medicine · 2025Review
- Discovery of First-in-Class Carbonic Anhydrase/Histone Deacetylase Dual Inhibitors with Antiproliferative Activity in Cancer Cells.Journal of medicinal chemistry · 2025Article
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- Integrating network pharmacology and experimental models to investigate the efficacy and mechanism of Tiansha mixture on xerosis.Archives of dermatological research · 2024Article
- Unveiling the Role of Tryptophan 2,3-Dioxygenase in the Angiogenic Process.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Iron Oxide Nanoparticles: Selectively Targeting Melanoma Cells In Vitro by Inducing DNA Damage via H2AX Phosphorylation and Hindering Proliferation through ERK Dephosphorylation.Pharmaceutics · 2024Article
- Antibody dependent cellular cytotoxicity-inducing anti-EGFR antibodies as effective therapeutic option for cutaneous melanoma resistant to BRAF inhibitors.Frontiers in immunology · 2024Article
- Redrawing Urokinase Receptor (uPAR) Signaling with Cancer Driver Genes for Exploring Possible Anti-Cancer Targets and Drugs.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Potential Biomarkers of Skin Melanoma Resistance to Targeted Therapy-Present State and Perspectives.Cancers · 2022Review
- Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer.Journal of translational medicine · 2022Review
- uPAR Controls Vasculogenic Mimicry Ability Expressed by Drug-Resistant Melanoma Cells.Oncology research · 2022Article
- Review
- Colon fibroblasts from Pirc rats (F344/NTac-ApcInternational journal of cancer · 2022Article
- RSK2 promotes melanoma cell proliferation and vemurafenib resistanceFrontiers in pharmacology · 2022Article
- Metastatic phenotype and immunosuppressive tumour microenvironment in pancreatic ductal adenocarcinoma: Key role of the urokinase plasminogen activator (PLAU).Frontiers in immunology · 2022Article
- uPARJournal for immunotherapy of cancer · 2021Article
- uPAR-expressing melanoma exosomes promote angiogenesis by VE-Cadherin, EGFR and uPAR overexpression and rise of ERK1,2 signaling in endothelial cells.Cellular and molecular life sciences : CMLS · 2021Article
- The Multifaceted Role of Plasminogen in Cancer.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBRAF inhibitor (BRAF-I) therapy for melanoma patients harboring the V600E mutation is initially highly effective, but almost all patients relapse within a few months. Understanding the molecular mechanisms behind BRAF-I responsiveness and acquired resistance is therefore an important issue. Here we assessed the role of urokinase type plasminogen activator receptor (uPAR) as a potentially valuable biomarker in the acquisition of BRAF-I resistance in V600E mutant melanoma cells.
methodsWe examined uPAR and EGFR levels by real time PCR and western blot analysis. uPAR loss of function was realized by knocking down uPAR by RNAi or using M25, a peptide that uncouples uPAR-integrin interaction. We investigated uPAR-β1integrin-EGFR association by co-immunoprecipitation and confocal immuno-fluorescence analysis. Acquired resistance to BRAF-I was generated by chronic exposure of cells to vemurafenib.
findingsWe proved that uPAR knockdown in combination with vemurafenib inhibits melanoma cell proliferation to greater extent than either treatment alone causing a decrease in AKT and ERK1/2 phosphorylation. Conversely, we demonstrated that uPAR enforced over-expression results in reduced sensitivity to BRAF inhibition. Moreover, by targeting uPAR and EGFR interaction with an integrin antagonist peptide we restored vemurafenib responsiveness in melanoma resistant cells. Furthermore, we found significant detectable uPAR and EGFR levels in tumor biopsies of 4 relapsed patients.
interpretationWe disclosed an unpredicted mechanism of reduced sensitiveness to BRAF inhibition, driven by elevated levels of uPAR and identified a potential therapeutic strategy to overcome acquired resistance. FUNDS: Associazione Italiana Ricerca sul Cancro (AIRC); Ente Cassa di Risparmio di Firenze.
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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 Socratic graph.