دورية أكاديمية
Blockade of the pro‐fibrotic reaction mediated by the miR‐143/‐145 cluster enhances the responses to targeted therapy in melanoma
| العنوان: | Blockade of the pro‐fibrotic reaction mediated by the miR‐143/‐145 cluster enhances the responses to targeted therapy in melanoma |
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| المؤلفون: | Diazzi, Serena, Baeri, Alberto, Fassy, Julien, Lecacheur, Margaux, Marin‐bejar, Oskar, Girard, Christophe, Lefevre, Lauren, Lacoux, Caroline, Irondelle, Marie, Mounier, Carine, Truchi, Marin, Couralet, Marie, Ohanna, Mickael, Carminati, Alexandrine, Berestjuk, Ilona, Larbret, Frederic, Gilot, David, Vassaux, Georges, Marine, Jean‐christophe, Deckert, Marcel, Mari, Bernard, Tartare‐deckert, Sophie |
| المساهمون: | Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UniCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven = Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie Ghent, Belgique (VIB), Catholic University of Leuven = Katholieke Universiteit Leuven (KU Leuven), Equipe de recherche sur les relations matrice extracellulaire-cellules (ERRMECe), Fédération INSTITUT DES MATÉRIAUX DE CERGY-PONTOISE (I-MAT), CY Cergy Paris Université (CY)-CY Cergy Paris Université (CY), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), FHU OncoAge - Pathologies liées à l’âge CHU Nice (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA), Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, #G.0929.16N, Fonds Wetenschappelijk Onderzoek, Centre National de la Recherche Scientifique, Ligue Contre le Cancer, INCA_12673, Institut National Du Cancer, ANR‐PRCI‐18‐CE92‐0009‐01, Agence Nationale de la Recherche, Canceropôle PACA, Fondation ARC pour la Recherche sur le Cancer, ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011) |
| المصدر: | ISSN: 1757-4676. |
| بيانات النشر: | HAL CCSD Wiley Open Access |
| سنة النشر: | 2022 |
| المجموعة: | Université de Rennes 1: Publications scientifiques (HAL) |
| مصطلحات موضوعية: | MAPK inhibitors, fibrosis, melanoma, microRNA, nintedanib, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Lineage dedifferentiation toward a mesenchymal-like state displaying myofibroblast and fibrotic features is a common mechanism of adaptive and acquired resistance to targeted therapy in melanoma. Here, we show that the anti-fibrotic drug nintedanib is active to normalize the fibrous ECM network, enhance the efficacy of MAPK-targeted therapy, and delay tumor relapse in a preclinical model of melanoma. Acquisition of this resistant phenotype and its reversion by nintedanib pointed to miR-143/-145 pro-fibrotic cluster as a driver of this mesenchymal-like phenotype. Upregulation of the miR-143/-145 cluster under BRAFi/MAPKi therapy was observed in melanoma cells in vitro and in vivo and was associated with an invasive/undifferentiated profile. The 2 mature miRNAs generated from this cluster, miR-143-3p and miR-145-5p, collaborated to mediate transition toward a drug-resistant undifferentiated mesenchymal-like state by targeting Fascin actin-bundling protein 1 (FSCN1), modulating the dynamic crosstalk between the actin cytoskeleton and the ECM through the regulation of focal adhesion dynamics and mechanotransduction pathways. Our study brings insights into a novel miRNA-mediated regulatory network that contributes to non-genetic adaptive drug resistance and provides proof of principle that preventing MAPKi-induced pro-fibrotic stromal response is a viable therapeutic opportunity for patients on targeted therapy. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35156321; inserm-03574667; https://inserm.hal.science/inserm-03574667Test; https://inserm.hal.science/inserm-03574667/documentTest; https://inserm.hal.science/inserm-03574667/file/EmboMolMed2022.pdfTest; PUBMED: 35156321 |
| DOI: | 10.15252/emmm.202115295 |
| الإتاحة: | https://doi.org/10.15252/emmm.202115295Test https://inserm.hal.science/inserm-03574667Test https://inserm.hal.science/inserm-03574667/documentTest https://inserm.hal.science/inserm-03574667/file/EmboMolMed2022.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.693BED |
| قاعدة البيانات: | BASE |
| DOI: | 10.15252/emmm.202115295 |
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