title: Specific unsaturated fatty acids enforce the transdifferentiation of human cancer cells toward adipocyte-like cells.
abstract: Differentiation therapy pursues the discovery of novel molecules to transform cancer progression into less aggressive phenotypes by mechanisms involving enforced cell transdifferentiation. In this study, we examined the identification of transdifferentiating adipogenic programs in human cancer cell lines (HCCLs). Our findings showed that specific unsatturated fatty acids, such as palmitoleic, oleic and linoleic acids, trigger remarkable phenotypic modifications in a large number of human cancer cell lines (HCCLs), including hepatocarcinoma HUH-7, ovarian carcinoma SK-OV-3, breast adenocarcinoma MCF-7 and melanoma MALME-3M. In particular, we characterized a massive biogenesis of lipid droplets (LDs) and up-regulation of the adipogenic master regulator, PPARG, resulting in the transdifferentiation of HCCLs into adipocyte-like cells. These findings suggest the possibility of a novel strategy in cancer differentiation therapy via switching the identity of HCCLs to an adipogenic phenotype through unsaturated fatty acid-induced transdifferentiation.
authors.affiliation: Valencia Node of the Spanish Stem Cell Bank, Prince Felipe Research Centre (CIPF), Avda. Autopista del Saler, 16-3, 46012 Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ruiz-Vela
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Aguilar-Gallardo
authors.forename: Ana M
authors.initials: AM
authors.lastname: Martínez-Arroyo
authors.forename: Mario
authors.initials: M
authors.lastname: Soriano-Navarro
authors.forename: Verónica
authors.initials: V
authors.lastname: Ruiz
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis; D000418:Albumins / Q000378:metabolism; D045744:Cell Line, Tumor; D054338:Cell Transdifferentiation; D017077:Culture Media, Conditioned / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D008041:Linoleic Acids / Q000378:metabolism; D009829:Oleic Acids / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D010641:Phenotype; D044967:Serum / Q000378:metabolism
chemical_list: D000418:Albumins; D017077:Culture Media, Conditioned; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D009829:Oleic Acids; D047495:PPAR gamma; C008757:palmitoleic acid; C008820:petroselinic acid