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dc.contributor.author | Marco-Brualla, Joaquín | |
dc.contributor.author | Al-Wasaby, Sameer | |
dc.contributor.author | Soler, Ruth | |
dc.contributor.author | Romanos, Eduardo | |
dc.contributor.author | Conde, Blanca | |
dc.contributor.author | Justo-Mendez, Raquel | |
dc.contributor.author | Enriquez, Jose Antonio | |
dc.contributor.author | Fernández-Silva, Patricio | |
dc.contributor.author | Martínez-Lostao, Luis | |
dc.contributor.author | Villalba, Martín | |
dc.contributor.author | Moreno-Loshuertos, Raquel | |
dc.contributor.author | Anel, Alberto | |
dc.date.accessioned | 2019-09-11T05:36:13Z | |
dc.date.available | 2019-09-11T05:36:13Z | |
dc.date.issued | 2019-07 | |
dc.identifier.citation | Cancers (Basel). 2019; 11(7):E1027 | es_ES |
dc.identifier.issn | 2072-6694 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/8327 | |
dc.description.abstract | Multiprotein 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.sponsorship | This 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 PHISIUP | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Multidisciplinary Digital Publishing Institute (MDPI) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | ND2 | es_ES |
dc.subject | Complex I | es_ES |
dc.subject | Cybrids | es_ES |
dc.subject | Dichloroacetate | es_ES |
dc.subject | Metastasis | es_ES |
dc.subject | Mitochondria | es_ES |
dc.title | Mutations in the ND2 Subunit of Mitochondrial Complex I Are Sufficient to Confer Increased Tumorigenic and Metastatic Potential to Cancer Cells | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 31330915 | es_ES |
dc.format.volume | 11 | es_ES |
dc.format.number | 7 | es_ES |
dc.format.page | 1027 | es_ES |
dc.identifier.doi | 10.3390/cancers11071027 | es_ES |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Gobierno de Aragón (España) | |
dc.contributor.funder | European Molecular Biology Organization | |
dc.description.peerreviewed | Sí | es_ES |
dc.relation.publisherversion | https://doi.org/10.3390/cancers11071027 | es_ES |
dc.identifier.journal | Cancers | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Genética Funcional del Sistema de Fosforilación Oxidativa | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2013-48626-C2-1-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2016-76338-R | es_ES |
dc.rights.accessRights | open access | es_ES |