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Discoidin Domain Receptor 2 orchestrates melanoma resistance combining phenotype switching and proliferation

dc.rights.licenseopenen_US
dc.contributor.authorSALA, Margaux
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorALLAIN, Nathalie
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorMOREAU, Mélanie
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorJABOUILLE, Arnaud
hal.structure.identifierJohns Hopkins University [JHU]
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorHENRIET, Elodie
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorABOU-HAMMOUD, Aya
hal.structure.identifierHôpital Morvan - CHRU de Brest [CHU - BREST ]
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorUGUEN, Arnaud
hal.structure.identifierTBM-Core [Bordeaux] [UMS3427 - INSERM US005]
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorDI-TOMMASO, Sylvaine
hal.structure.identifierTBM-Core [Bordeaux] [UMS3427 - INSERM US005]
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorDOURTHE, Cyril
hal.structure.identifierTBM-Core [Bordeaux] [UMS3427 - INSERM US005]
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorRAYMOND, Anne-Aurélie
dc.contributor.authorDUPUY, Jean-William
dc.contributor.authorGERARD, Emilie
hal.structure.identifierTBM-Core [Bordeaux] [UMS3427 - INSERM US005]
dc.contributor.authorDUGOT-SENANT, Nathalie
hal.structure.identifierUniversité de Bordeaux [UB]
dc.contributor.authorROUSSEAU, Benoit
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
hal.structure.identifierCHU Bordeaux
dc.contributor.authorMERLIO, Jean-Phillipe
hal.structure.identifierCHU Bordeaux
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorPHAM-LEDART, Anne
hal.structure.identifierCHU Bordeaux
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorVERGIER, Béatrice
dc.contributor.authorTARTARE-DECKERT, Sophie
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorMOREAU, Violaine
hal.structure.identifierTBM-Core [Bordeaux] [UMS3427 - INSERM US005]
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorSALTEL, Frédéric
dc.date.accessioned2023-05-15T10:38:00Z
dc.date.available2023-05-15T10:38:00Z
dc.date.issued2022-04-29
dc.identifier.issn0950-9232en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182126
dc.description.abstractEnCombined therapy with anti-BRAF plus anti-MEK is currently used as first-line treatment of patients with metastatic melanomas harboring the somatic BRAF V600E mutation. However, the main issue with targeted therapy is the acquisition of tumor cell resistance. In a majority of resistant melanoma cells, the resistant process consists in epithelial-to-mesenchymal transition (EMT). This process called phenotype switching makes melanoma cells more invasive. Its signature is characterized by MITF low, AXL high, and actin cytoskeleton reorganization through RhoA activation. In parallel of this phenotype switching phase, the resistant cells exhibit an anarchic cell proliferation due to hyper-activation of the MAP kinase pathway. We show that a majority of human melanoma overexpress discoidin domain receptor 2 (DDR2) after treatment. The same result was found in resistant cell lines presenting phenotype switching compared to the corresponding sensitive cell lines. We demonstrate that DDR2 inhibition induces a decrease in AXL expression and reduces stress fiber formation in resistant melanoma cell lines. In this phenotype switching context, we report that DDR2 control cell and tumor proliferation through the MAP kinase pathway in resistant cells in vitro and in vivo. Therefore, inhibition of DDR2 could be a new and promising strategy for countering this resistance mechanism.
dc.language.isoENen_US
dc.subject.meshCell Line, Tumor
dc.subject.meshCell Proliferation
dc.subject.meshDiscoidin Domain Receptor 2
dc.subject.meshDrug Resistance, Neoplasm
dc.subject.meshHumans
dc.subject.meshMelanoma
dc.subject.meshPhenotype
dc.subject.meshProtein Kinase Inhibitors
dc.subject.meshProto-Oncogene Proteins B-raf
dc.title.enDiscoidin Domain Receptor 2 orchestrates melanoma resistance combining phenotype switching and proliferation
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41388-022-02266-1en_US
dc.subject.halSciences du Vivant [q-bio]en_US
bordeaux.journalOncogeneen_US
bordeaux.page2571-2586en_US
bordeaux.volume41en_US
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.issue18en_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierinserm-03791558
hal.version1
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Oncogene&rft.date=2022-04-29&rft.volume=41&rft.issue=18&rft.spage=2571-2586&rft.epage=2571-2586&rft.eissn=0950-9232&rft.issn=0950-9232&rft.au=SALA,%20Margaux&ALLAIN,%20Nathalie&MOREAU,%20M%C3%A9lanie&JABOUILLE,%20Arnaud&HENRIET,%20Elodie&rft.genre=article


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