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dc.contributor.authorMarco-Brualla, Joaquín
dc.contributor.authorAl-Wasaby, Sameer
dc.contributor.authorSoler, Ruth
dc.contributor.authorRomanos, Eduardo
dc.contributor.authorConde, Blanca
dc.contributor.authorJusto-Mendez, Raquel 
dc.contributor.authorEnriquez, Jose Antonio 
dc.contributor.authorFernández-Silva, Patricio
dc.contributor.authorMartínez-Lostao, Luis
dc.contributor.authorVillalba, Martín
dc.contributor.authorMoreno-Loshuertos, Raquel
dc.contributor.authorAnel, Alberto
dc.date.accessioned2019-09-11T05:36:13Z
dc.date.available2019-09-11T05:36:13Z
dc.date.issued2019-07
dc.identifier.citationCancers (Basel). 2019; 11(7):E1027es_ES
dc.identifier.issn2072-6694es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/8327
dc.description.abstractMultiprotein complexes of the mitochondrial electron transport chain form associations to generate supercomplexes. The relationship between tumor cell ability to assemble mitochondrial supercomplexes, tumorigenesis and metastasis has not been studied thoroughly. The mitochondrial and metabolic differences between L929dt cells, which lost matrix attachment and MHC-I expression, and their parental cell line L929, were analyzed. L929dt cells have lower capacity to generate energy through OXPHOS and lower respiratory capacity than parental L929 cells. Most importantly, L929dt cells show defects in mitochondrial supercomplex assembly, especially in those that contain complex I. These defects correlate with mtDNA mutations in L929dt cells at the ND2 subunit of complex I and are accompanied by a glycolytic shift. In addition, L929dt cells show higher in vivo tumorigenic and metastatic potential than the parental cell line. Cybrids with L929dt mitochondria in L929 nuclear background reproduce all L929dt properties, demonstrating that mitochondrial mutations are responsible for the aggressive tumor phenotype. In spite of their higher tumorigenic potential, L929dt or mitochondrial L929dt cybrid cells are sensitive both in vitro and in vivo to the PDK1 inhibitor dichloroacetate, which favors OXPHOS, suggesting benefits for the use of metabolic inhibitors in the treatment of especially aggressive tumors.es_ES
dc.description.sponsorshipThis work was supported by grants SAF2013-48626-C2-1-R and SAF2016-76338-R from Ministerio de Economía y Competitividad (MINECO) to AA, by the PRT-K program 2018 to MV and by Gobierno de Aragón (Group B31_17R) cofinanced by Feder 2014-2020 “Building Europe from Aragon”. JMB was supported by an EMBO short-term fellowship and by PHISIUPes_ES
dc.language.isoenges_ES
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI) es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectND2es_ES
dc.subjectComplex Ies_ES
dc.subjectCybridses_ES
dc.subjectDichloroacetatees_ES
dc.subjectMetastasises_ES
dc.subjectMitochondriaes_ES
dc.titleMutations in the ND2 Subunit of Mitochondrial Complex I Are Sufficient to Confer Increased Tumorigenic and Metastatic Potential to Cancer Cellses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID31330915es_ES
dc.format.volume11es_ES
dc.format.number7es_ES
dc.format.page1027es_ES
dc.identifier.doi10.3390/cancers11071027es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderGobierno de Aragón (España) 
dc.contributor.funderEuropean Molecular Biology Organization 
dc.description.peerreviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.3390/cancers11071027es_ES
dc.identifier.journalCancerses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Genética Funcional del Sistema de Fosforilación Oxidativaes_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2013-48626-C2-1-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2016-76338-Res_ES
dc.rights.accessRightsopen accesses_ES


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