Midkine signaling maintains the self-renewal and tumorigenic capacity of glioma initiating cells

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dc.contributor.authorLópez Valero, Israel
dc.contributor.authorDávila, David
dc.contributor.authorGonzález Martínez, José
dc.contributor.authorSalvador-Tormo, Nélida
dc.contributor.authorLorente Pérez, María Del Mar
dc.contributor.authorSaiz Ladera, Cristina
dc.contributor.authorTorres Pabón, Norma Sofía
dc.contributor.authorGabicagogeascoa Corta, Estíbaliz
dc.contributor.authorHernández-Tiedra, Sonia
dc.contributor.authorGarcía Taboada, Elena
dc.contributor.authorMendiburu Eliçabe, Marina
dc.contributor.authorRodríguez Fornés, Fátima
dc.contributor.authorSánchez Domínguez, Rebeca
dc.contributor.authorSegovia Martínez, Juan Carlos
dc.contributor.authorSánchez Gómez, Pilar
dc.contributor.authorMatheu Fernández, Ander
dc.contributor.authorSepúlveda Salas, Juan Miguel
dc.contributor.authorVelasco Díez, Guillermo
dc.date.accessioned2023-06-16T15:18:50Z
dc.date.available2023-06-16T15:18:50Z
dc.date.issued2020-04-06
dc.description.abstractGlioblastoma (GBM) is one of the most aggressive forms of cancer. It has been proposed that the presence within these tumors of a population of cells with stem-like features termed Glioma Initiating Cells (GICs) is responsible for the relapses that take place in the patients with this disease. Targeting this cell population is therefore an issue of great therapeutic interest in neuro-oncology. We had previously found that the neurotrophic factor MIDKINE (MDK) promotes resistance to glioma cell death. The main objective of this work is therefore investigating the role of MDK in the regulation of GICs. Methods: Assays of gene and protein expression, self-renewal capacity, autophagy and apoptosis in cultures of GICs derived from GBM samples subjected to different treatments. Analysis of the growth of GICs-derived xenografts generated in mice upon blockade of the MDK and its receptor the ALK receptor tyrosine kinase (ALK) upon exposure to different treatments. Results: Genetic or pharmacological inhibition of MDK or ALK decreases the self-renewal and tumorigenic capacity of GICs via the autophagic degradation of the transcription factor SOX9. Blockade of the MDK/ALK axis in combination with temozolomide depletes the population of GICs in vitro and has a potent anticancer activity in xenografts derived from GICs. Conclusions: The MDK/ALK axis regulates the self-renewal capacity of GICs by controlling the autophagic degradation of the transcription factor SOX9. Inhibition of the MDK/ALK axis may be a therapeutic strategy to target GICs in GBM patients.eng
dc.description.departmentSección Deptal. de Bioquímica y Biología Molecular (Biológicas)
dc.description.facultyFac. de Ciencias Biológicas
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Economía y Competitividad (España)
dc.description.sponsorshipPlan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020
dc.description.sponsorshipInstituto de Salud Carlos III
dc.description.sponsorshipFundación Mutua Madrileña
dc.description.sponsorshipFundació La Marató de TV3
dc.description.sponsorshipAsociación Española contra el Cáncer
dc.description.sponsorshipVoices Against Brain Cancer
dc.description.sponsorshipThe Medical Cannabis Bike Tour Foundation(Netherlands)
dc.description.sponsorshipFederación Española de Enfermedades Raras
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/60826
dc.identifier.citationLópez-Valero I, Dávila D, González-Martínez J, Salvador-Tormo N, Lorente M, Saiz-Ladera C, et al. Midkine signaling maintains the self-renewal and tumorigenic capacity of glioma initiating cells. Theranostics 2020;10:5120–36. https://doi.org/10.7150/thno.41450.
dc.identifier.doi10.7150/thno.41450
dc.identifier.essn1838-7640
dc.identifier.officialurlhttps://doi.org/10.7150/thno.41450
dc.identifier.urihttps://hdl.handle.net/20.500.14352/6308
dc.issue.number11
dc.journal.titleTheranostics
dc.language.isoeng
dc.page.final5136
dc.page.initial5120
dc.publisherIvyspring International Publisher
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/SAF2015-65175-R/ERDF
dc.relation.projectIDinfo:eu-repo/grantAgreement/PI18/00442
dc.relation.projectIDinfo:eu-repo/grantAgreement/PS09/01401
dc.relation.projectIDinfo:eu-repo/grantAgreement/AP101042012
dc.relation.projectIDinfo:eu-repo/grantAgreement/20134031
dc.relation.projectIDinfo:eu-repo/grantAgreement/GCTRA16015SEDA
dc.relation.projectIDinfo:eu-repo/grantAgreement/PI12/02248;PI15/00339
dc.relation.projectIDinfo:eu-repo/grantAgreement/PI16/01580
dc.relation.projectIDinfo:eu-repo/grantAgreement/PI16/01278
dc.relation.projectIDinfo:eu-repo/grantAgreement/CP16/00039
dc.rightsATTRIBUTION 4.0 INTERNATIONAL
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.cdu577.112
dc.subject.cdu577.2
dc.subject.cdu616-006.04
dc.subject.keywordGlioblastoma
dc.subject.keywordMidkine
dc.subject.keywordALK receptor tyrosine kinase
dc.subject.keywordAutophagy
dc.subject.keywordSOX
dc.subject.keywordCombinational therapies
dc.subject.ucmOncología
dc.subject.ucmBiología molecular (Biología)
dc.subject.ucmBioquímica (Biología)
dc.subject.unesco3201.01 Oncología
dc.subject.unesco2415 Biología Molecular
dc.subject.unesco2302 Bioquímica
dc.titleMidkine signaling maintains the self-renewal and tumorigenic capacity of glioma initiating cells
dc.typejournal article
dc.volume.number10
dspace.entity.typePublication
relation.isAuthorOfPublication974345b1-6b30-49ae-9724-2e4714f80000
relation.isAuthorOfPublication.latestForDiscovery974345b1-6b30-49ae-9724-2e4714f80000
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