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dc.contributor.authorGuyon, Joris
dc.contributor.authorFernandez-Moncada, Ignacio
dc.contributor.authorLarrieu, Claire M
dc.contributor.authorBouchez, Cyrielle L
dc.contributor.authorPagano Zottola, Antonio C
dc.contributor.authorGalvis, Johanna
dc.contributor.authorChouleur, Tiffanie
dc.contributor.authorBurban, Audrey
dc.contributor.authorJoseph, Kevin
dc.contributor.authorRavi, Vidhya M
dc.contributor.authorEspedal, Heidi
dc.contributor.authorRøsland, Gro Vatne
dc.contributor.authorDaher, Boutaina
dc.contributor.authorBarre, Aurélien
dc.contributor.authorDartigues, Benjamin
dc.contributor.authorKarkar, Slim
dc.contributor.authorRudewicz, Justine
dc.contributor.authorRomero-Garmendia, Irati
dc.contributor.authorKlink, Barbara
dc.contributor.authorGrützmann, Konrad
dc.contributor.authorDerieppe, Marie-Alix
dc.contributor.authorMolinié, Thibaut
dc.contributor.authorObad, Nina
dc.contributor.authorLéon, Céline
dc.contributor.authorSeano, Giorgio
dc.contributor.authorMiletic, Hrvoje
dc.contributor.authorHeiland, Dieter Henrik
dc.contributor.authorMarsicano, Giovanni
dc.contributor.authorNikolski, Macha
dc.contributor.authorBjerkvig, Rolf
dc.contributor.authorBikfalvi, Andreas
dc.contributor.authorDaubon, Thomas
dc.description.abstractLactate is a central metabolite in brain physiology but also contributes to tumor development. Glioblastoma (GB) is the most common and malignant primary brain tumor in adults, recognized by angiogenic and invasive growth, in addition to its altered metabolism. We show herein that lactate fuels GB anaplerosis by replenishing the tricarboxylic acid (TCA) cycle in absence of glucose. Lactate dehydrogenases (LDHA and LDHB), which we found spatially expressed in GB tissues, catalyze the interconversion of pyruvate and lactate. However, ablation of both LDH isoforms, but not only one, led to a reduction in tumor growth and an increase in mouse survival. Comparative transcriptomics and metabolomics revealed metabolic rewiring involving high oxidative phosphorylation (OXPHOS) in the LDHA/B KO group which sensitized tumors to cranial irradiation, thus improving mouse survival. When mice were treated with the antiepileptic drug stiripentol, which targets LDH activity, tumor growth decreased. Our findings unveil the complex metabolic network in which both LDHA and LDHB are integrated and show that the combined inhibition of LDHA and LDHB strongly sensitizes GB to therapy.en_US
dc.publisherEmbo Pressen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleLactate dehydrogenases promote glioblastoma growth and invasion via a metabolic symbiosisen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.source.journalEMBO Molecular Medicineen_US
dc.identifier.citationEMBO Molecular Medicine. 2022, 14, e15343.en_US

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