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Targeting the mitochondrial trifunctional protein restrains tumor growth in oxidative lung carcinomas

dc.rights.licenseopenen_US
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorAMOEDO, Nivea Dias
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorSARLAK, Saharnaz
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorOBRE, Emilie
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorESTEVES, Pauline
dc.contributor.authorBEGUERET, Hugues
dc.contributor.authorKIEFFER, Yann
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorROUSSEAU, Benoit
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorDUPIS, Alexis
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorIZOTTE, Julien
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorBELLANCE, Nadege
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorDARD, Laetitia
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorREDONNET VERNHET, Isabelle
dc.contributor.authorPUNZI, Giuseppe
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorRODRIGUES, Mariana Figueiredo
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorDUMON, Elodie
hal.structure.identifierBiothérapies des maladies génétiques et cancers
dc.contributor.authorMAFHOUF, Walid
dc.contributor.authorGUYONNET-DUPERAT, Veronique
dc.contributor.authorGALES, Lara
dc.contributor.authorPALAMA, Tony
dc.contributor.authorBELLVERT, Floriant
dc.contributor.authorDUGOT-SENAN, Nathalie
dc.contributor.authorCLAVEROL, Stephane
dc.contributor.authorBASTE, Jean-Marc
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorLACOMBE, Didier
hal.structure.identifierBiothérapies des maladies génétiques et cancers
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorREZVANI, Hamid Reza
dc.contributor.authorPIERRI, Ciro Leonardo
dc.contributor.authorMECHTA-GRIGORIOU, Fatima
dc.contributor.authorTHUMEREL, Matthieu
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorROSSIGNOL, Rodrigue
dc.date.accessioned2021-10-26T15:24:23Z
dc.date.available2021-10-26T15:24:23Z
dc.date.issued2021-01-04
dc.identifier.issn1365-2362en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/117085
dc.description.abstractEnMetabolic reprogramming is a common hallmark of cancer, but a large variability in tumor bioenergetics exists between patients. Using high-resolution respirometry on fresh biopsies of human lung adenocarcinoma, we identified 2 subgroups reflected in the histologically normal, paired, cancer-adjacent tissue: High (OX+) mitochondrial respiration and low (OX-) mitochondrial respiration. The OX+ tumors poorly incorporated [18F]fluorodeoxy-glucose and showed increased expression of the mitochondrial trifunctional fatty acid oxidation enzyme (MTP; HADHA) compared with the paired adjacent tissue. Genetic inhibition of MTP altered OX+ tumor growth in vivo. Trimetazidine, an approved drug inhibitor of MTP used in cardiology, also reduced tumor growth and induced disruption of the physical interaction between the MTP and respiratory chain complex I, leading to a cellular redox and energy crisis. MTP expression in tumors was assessed using histology scoring methods and varied in negative correlation with [18F]fluorodeoxy-glucose incorporation. These findings provide proof-of-concept data for preclinical, precision, bioenergetic medicine in oxidative lung carcinomas.
dc.language.isoENen_US
dc.title.enTargeting the mitochondrial trifunctional protein restrains tumor growth in oxidative lung carcinomas
dc.typeArticle de revueen_US
dc.identifier.doi10.1172/JCI133081en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
dc.identifier.pubmed33393495en_US
bordeaux.journalJournal of Clinical Investigationen_US
bordeaux.volume131en_US
bordeaux.hal.laboratoriesMaladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDInstitut National de la Santé et de la Recherche Médicaleen_US
bordeaux.identifier.funderIDFondation ARC pour la Recherche sur le Canceren_US
bordeaux.identifier.funderIDPlan National Canceren_US
bordeaux.identifier.funderIDInstitut National Du Canceren_US
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
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