{ "dc.contributor.author": "Corominas Faja, Bruna" , "dc.contributor.author": "Cuyàs, Elisabet" , "dc.contributor.author": "Gumuzio, Juan" , "dc.contributor.author": "Bosch Barrera, Joaquim" , "dc.contributor.author": "Leis, Olatz" , "dc.contributor.author": "Martin, Ángel G." , "dc.contributor.author": "Menéndez Menéndez, Javier Abel" , "dc.date.accessioned": "2018-12-18T07:59:16Z" , "dc.date.available": "2018-12-18T07:59:16Z" , "dc.date.issued": "2014" , "dc.identifier.issn": "1949-2553" , "dc.identifier.uri": "http://hdl.handle.net/10256/16145" , "dc.description.abstract": "Cancer stem cells (CSC) may take advantage of the Warburg effect-induced siphoning of metabolic intermediates into de novo fatty acid biosynthesis to increase self-renewal growth. We examined the anti-CSC effects of the antifungal polyketide soraphen A, a specific inhibitor of the first committed step of lipid biosynthesis catalyzed by acetyl-CoA carboxylase (ACACA). The mammosphere formation capability of MCF-7 cells was reduced following treatment with soraphen A in a dose-dependent manner. MCF-7 cells engineered to overexpress the oncogene HER2 (MCF-7/HER2 cells) were 5-fold more sensitive than MCF-7 parental cells to soraphen A-induced reductions in mammosphere-forming efficiency. Soraphen A treatment notably decreased aldehyde dehydrogenase (ALDH)-positive CSC-like cells and impeded the HER2’s ability to increase the ALDH+-stem cell population. The following results confirmed that soraphen A-induced suppression of CSC populations occurred throughACACA-driven lipogenesis: a.) exogenous supplementation with supraphysiological concentrations of oleic acid fully rescued mammosphere formation in the presence of soraphen A and b.) mammosphere cultures of MCF-7 cells with stably silenced expression of the cytosolic isoform ACACA1, which specifically participates in de novo lipogenesis, were mostly refractory to soraphen A treatment. Our findings reveal for the first time that ACACA may constitute a previously unrecognized target for novel anti-breast CSC therapies" , "dc.format.mimetype": "application/pdf" , "dc.language.iso": "eng" , "dc.publisher": "Impact Journals" , "dc.relation.isformatof": "Reproducció digital del document publicat a: https://doi.org/10.18632/oncotarget.2059" , "dc.relation.ispartof": "Oncotarget, 2014, vol. 5, núm. 18, p. 8306-8316" , "dc.relation.ispartofseries": "Articles publicats (IdIBGi)" , "dc.rights": "Reconeixement 3.0 Espanya" , "dc.rights.uri": "http://creativecommons.org/licenses/by/3.0/es/deed.ca" , "dc.subject": "Mama -- Càncer" , "dc.subject": "Breast -- Cancer" , "dc.subject": "Cèl·lules mare -- Càncer" , "dc.subject": "Stem cells -- Cancer" , "dc.title": "Chemical inhibition of acetyl-CoA carboxylase suppresses self-renewal growth of cancer stem cells" , "dc.type": "info:eu-repo/semantics/article" , "dc.rights.accessRights": "info:eu-repo/semantics/openAccess" , "dc.type.version": "info:eu-repo/semantics/publishedVersion" , "dc.identifier.doi": "https://doi.org/10.18632/oncotarget.2059" , "dc.identifier.idgrec": "024730" , "dc.type.peerreviewed": "peer-reviewed" }