Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma

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dc.contributor.authorOrtiz Ruiz, Alejandra
dc.contributor.authorRuiz Heredia, Yanira
dc.contributor.authorMorales, María Luz
dc.contributor.authorAguilar Garrido, Pedro
dc.contributor.authorGarcía Ortiz, Almudena
dc.contributor.authorValeri Lozano, Antonio
dc.contributor.authorBárcena Asensio, Carmen
dc.contributor.authorGarcía Martín, Rosa María
dc.contributor.authorGarrido, Vanesa
dc.contributor.authorMoreno Gutiérrez, Laura
dc.contributor.authorGimenez, Alicia
dc.contributor.authorNavarro Aguadero, Miguel Ángel
dc.contributor.authorVelasco Estévez, María
dc.contributor.authorLospitao, Eva
dc.contributor.authorCedena, María Teresa
dc.contributor.authorBarrio, Santiago
dc.contributor.authorMartínez López, Joaquín
dc.contributor.authorLinares Gómez, María
dc.contributor.authorGallardo, Miguel
dc.date.accessioned2023-06-17T08:23:03Z
dc.date.available2023-06-17T08:23:03Z
dc.date.issued2021-04-01
dc.description.abstractMitochondria are involved in the development and acquisition of a malignant phenotype in hematological cancers. Recently, their role in the pathogenesis of multiple myeloma (MM) has been suggested to be therapeutically explored. MYC is a master regulator of b-cell malignancies such as multiple myeloma, and its activation is known to deregulate mitochondrial function. We investigated the impact of mitochondrial activity on the distinct entities of the disease and tested the efficacy of the mitochondrial inhibitor, tigecycline, to overcome MM proliferation. COXII expression, COX activity, mitochondrial mass, and mitochondrial membrane potential demonstrated a progressive increase of mitochondrial features as the disease progresses. In vitro and in vivo therapeutic targeting using the mitochondrial inhibitor tigecycline showed promising efficacy and cytotoxicity in monotherapy and combination with the MM frontline treatment bortezomib. Overall, our findings demonstrate how mitochondrial activity emerges in MM transformation and disease progression and the efficacy of therapies targeting these novel vulnerabilities.
dc.description.departmentSección Deptal. de Bioquímica y Biología Molecular (Farmacia)
dc.description.departmentDepto. de Medicina
dc.description.facultyFac. de Farmacia
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.sponsorshipInstituto de Salud Carlos III (ISCIII)/ MINECO/ FEDER
dc.description.sponsorshipCRIS contra el Cancer Foundation, AECC
dc.description.sponsorshipComunidad de Madrid
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/70922
dc.identifier.doi10.3390/cancers13071662
dc.identifier.issn2072-6694
dc.identifier.officialurlhttps://doi.org/10.3390/cancers13071662
dc.identifier.relatedurlhttps://www.mdpi.com/2072-6694/13/7/1662/htm
dc.identifier.urihttps://hdl.handle.net/20.500.14352/6886
dc.issue.number7
dc.journal.titleCancers
dc.language.isoeng
dc.page.initial1662
dc.publisherMPDI
dc.relation.projectIDPI 18/00295, PI18/01519 and CP19/00140
dc.relation.projectID(INVES19015GALL)
dc.relation.projectID(PEJD-2017-PRE/BMD-4835 and PEJD-2019-POST/BMD-14505)
dc.rightsAtribución 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/es/
dc.subject.keywordmultiple myeloma
dc.subject.keywordmitochondria
dc.subject.keywordtigecycline
dc.subject.keywordMYC
dc.subject.ucmHematología
dc.subject.ucmOncología
dc.subject.ucmBiología celular (Biología)
dc.subject.unesco3205.04 Hematología
dc.subject.unesco3201.01 Oncología
dc.subject.unesco2407 Biología Celular
dc.titleMyc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma
dc.typejournal article
dc.volume.number13
dspace.entity.typePublication
relation.isAuthorOfPublication82925e82-9bdc-4f6a-8b54-2f83479c308b
relation.isAuthorOfPublication5d58b324-f60e-4598-941b-4a07291634a9
relation.isAuthorOfPublication855e6962-3ee2-4fc3-b110-96f1c20c5269
relation.isAuthorOfPublication.latestForDiscovery82925e82-9bdc-4f6a-8b54-2f83479c308b
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