2026-04-03T22:17:25Zhttps://recercat.cat/oai/request

oai:recercat.cat:10256/161452024-06-18T12:40:26Zcom_2072_452955com_2072_2054col_2072_453079

Chemical inhibition of acetyl-CoA carboxylase suppresses self-renewal growth of cancer stem cells Corominas Faja, Bruna Cuyàs, Elisabet Gumuzio, Juan Bosch Barrera, Joaquim Leis, Olatz Martin, Ángel G. Menéndez Menéndez, Javier Abel Mama -- Càncer Breast -- Cancer Cèl·lules mare -- Càncer Stem cells -- Cancer 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 2014 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion peer-reviewed http://hdl.handle.net/10256/16145 http://hdl.handle.net/10256/16145 eng info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.2059 info:eu-repo/semantics/altIdentifier/issn/1949-2553 Reconeixement 3.0 Espanya http://creativecommons.org/licenses/by/3.0/es/deed.ca info:eu-repo/semantics/openAccess application/pdf Impact Journals Oncotarget, 2014, vol. 5, núm. 18, p. 8306-8316 Articles publicats (IdIBGi)