000086368 001__ 86368
000086368 005__ 20200909105806.0
000086368 0247_ $$2doi$$a10.3390/cancers11071027
000086368 0248_ $$2sideral$$a115029
000086368 037__ $$aART-2019-115029
000086368 041__ $$aeng
000086368 100__ $$aMarco-Brualla, Joaquín
000086368 245__ $$aMutations in the ND2 subunit of mitochondrial complex I are sufficient to confer increased tumorigenic and metastatic potential to cancer cells
000086368 260__ $$c2019
000086368 5060_ $$aAccess copy available to the general public$$fUnrestricted
000086368 5203_ $$aMultiprotein 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.
000086368 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B31-17R$$9info:eu-repo/grantAgreement/ES/MICINN/SAF2013-48626-C2-1-R$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2016-76338-R
000086368 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000086368 590__ $$a6.126$$b2019
000086368 591__ $$aONCOLOGY$$b37 / 244 = 0.152$$c2019$$dQ1$$eT1
000086368 592__ $$a1.938$$b2019
000086368 593__ $$aOncology$$c2019$$dQ1
000086368 593__ $$aCancer Research$$c2019$$dQ1
000086368 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000086368 700__ $$aAl-Wasaby, Sameer
000086368 700__ $$aSoler, Ruth
000086368 700__ $$aRomanos, Eduardo
000086368 700__ $$0(orcid)0000-0003-4115-9766$$aConde, Blanca$$uUniversidad de Zaragoza
000086368 700__ $$aJusto-Méndez, Raquel
000086368 700__ $$aEnríquez, José A.
000086368 700__ $$0(orcid)0000-0001-8971-7355$$aFernández-Silva, Patricio$$uUniversidad de Zaragoza
000086368 700__ $$0(orcid)0000-0003-3043-147X$$aMartínez-Lostao, Luis$$uUniversidad de Zaragoza
000086368 700__ $$aVillalba, Martín
000086368 700__ $$0(orcid)0000-0002-6600-1618$$aMoreno-Loshuertos, Raquel$$uUniversidad de Zaragoza
000086368 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, Alberto$$uUniversidad de Zaragoza
000086368 7102_ $$11003$$2443$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Histología
000086368 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Inmunología
000086368 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000086368 773__ $$g11, 7 (2019), 1027 [20 pp.]$$pCancers$$tCancers$$x2072-6694
000086368 8564_ $$s4162560$$uhttps://zaguan.unizar.es/record/86368/files/texto_completo.pdf$$yVersión publicada
000086368 8564_ $$s106487$$uhttps://zaguan.unizar.es/record/86368/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000086368 909CO $$ooai:zaguan.unizar.es:86368$$particulos$$pdriver
000086368 951__ $$a2020-09-09-10:50:02
000086368 980__ $$aARTICLE