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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorPerrone, Clara
dc.contributor.authorPomella, Silvia
dc.contributor.authorCassandri, Matteo
dc.contributor.authorPezzella, Michele
dc.contributor.authorMilano, Giuseppe Maria
dc.contributor.authorColletti, Marta
dc.contributor.authorRoma Castanyer, Josep
dc.contributor.authorGallego Melcón, Soledad
dc.date.accessioned2022-09-09T08:21:14Z
dc.date.available2022-09-09T08:21:14Z
dc.date.issued2022-04-27
dc.identifier.citationPerrone C, Pomella S, Cassandri M, Pezzella M, Milano GM, Colletti M, et al. MET Inhibition Sensitizes Rhabdomyosarcoma Cells to NOTCH Signaling Suppression. Front Oncol. 2022 Apr 27;12:835642.
dc.identifier.issn2234-943X
dc.identifier.urihttp://hdl.handle.net/11351/8095
dc.descriptionDrug resistance; Soft tissue sarcoma; Targeted therapy
dc.description.abstractRhabdomyosarcoma (RMS) is a pediatric myogenic soft tissue sarcoma. The Fusion-Positive (FP) subtype expresses the chimeric protein PAX3-FOXO1 (P3F) while the Fusion-Negative (FN) is devoid of any gene translocation. FP-RMS and metastatic FN-RMS are often unresponsive to conventional therapy. Therefore, novel therapeutic approaches are needed to halt tumor progression. NOTCH signaling has oncogenic functions in RMS and its pharmacologic inhibition through γ-secretase inhibitors blocks tumor growth in vitro and in vivo. Here, we show that NOTCH signaling blockade resulted in the up-regulation and phosphorylation of the MET oncogene in both RH30 (FP-RMS) and RD (FN-RMS) cell lines. Pharmacologic inhibition of either NOTCH or MET signaling slowed proliferation and restrained cell survival compared to control cells partly by increasing Annexin V and CASP3/7 activation. Co-treatment with NOTCH and MET inhibitors significantly amplified these effects and enhanced PARP1 cleavage in both cell lines. Moreover, it severely hampered cell migration, colony formation, and anchorage-independent growth compared to single-agent treatments in both cell lines and significantly prevented the growth of FN-RMS cells grown as spheroids. Collectively, our results unveil the overexpression of the MET oncogene by NOTCH signaling targeting in RMS cells and show that MET pathway blockade sensitizes them to NOTCH inhibition.
dc.language.isoeng
dc.publisherFrontiers Media
dc.relation.ispartofseriesFrontiers in Oncology;12
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectTumors de parts toves - Tractament
dc.subjectPediatria
dc.subjectProteïnes quinases - Inhibidors
dc.subject.meshRhabdomyosarcoma
dc.subject.mesh/drug therapy
dc.subject.meshPediatrics
dc.subject.meshProtein Kinase Inhibitors
dc.titleMET Inhibition Sensitizes Rhabdomyosarcoma Cells to NOTCH Signaling Suppression
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.3389/fonc.2022.835642
dc.subject.decsrabdomiosarcoma
dc.subject.decs/farmacoterapia
dc.subject.decspediatría
dc.subject.decsinhibidores de proteínas cinasas
dc.relation.publishversionhttps://doi.org/10.3389/fonc.2022.835642
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Perrone C] Department of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy. Department of Science, “Department of Excellence 2018-2022”, University of Rome “Roma Tre”, Rome, Italy. [Pomella S, Pezzella M, Milano GM, Colletti M] Department of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy. [Cassandri M] Department of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy. Department of Radiotherapy, Sapienza University, Rome, Italy. [Roma J, Gallego S] Grup de Recerca Translacional en Càncer en la Infància i l’Adolescència, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain
dc.identifier.pmid35574376
dc.identifier.wos000795729000001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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