2026-04-13T01:42:23Zhttps://recercat.cat/oai/request

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

00925njm 22002777a 4500 dc Corominas Faja, Bruna author Cuyàs, Elisabet author Gumuzio, Juan author Bosch Barrera, Joaquim author Leis, Olatz author Martin, Ángel G. author Menéndez Menéndez, Javier Abel author 2014 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 http://hdl.handle.net/10256/16145 Mama -- Càncer Breast -- Cancer Cèl·lules mare -- Càncer Stem cells -- Cancer Chemical inhibition of acetyl-CoA carboxylase suppresses self-renewal growth of cancer stem cells