Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/9317
Título
Essentiality of fatty acid synthase in the 2D to anchorage-independent growth transition in transforming cells
Autor(es)
Fecha de publicación
2019-11-01
Cita
Nat Commun. 2019 ;10(1):5011
Idioma
Inglés
Tipo de documento
journal article
Resumen
Upregulation of fatty acid synthase (FASN) is a common event in cancer, although its mechanistic and potential therapeutic roles are not completely understood. In this study, we establish a key role of FASN during transformation. FASN is required for eliciting the anaplerotic shift of the Krebs cycle observed in cancer cells. However, its main role is to consume acetyl-CoA, which unlocks isocitrate dehydrogenase (IDH)-dependent reductive carboxylation, producing the reductive power necessary to quench reactive oxygen species (ROS) originated during the switch from two-dimensional (2D) to three-dimensional (3D) growth (a necessary hallmark of cancer). Upregulation of FASN elicits the 2D-to-3D switch; however, FASN's synthetic product palmitate is dispensable for this process since cells satisfy their fatty acid requirements from the media. In vivo, genetic deletion or pharmacologic inhibition of FASN before oncogenic activation prevents tumor development and invasive growth. These results render FASN as a potential target for cancer prevention studies.
MESH
Animals | Cell Line | Cells, Cultured | Embryo, Mammalian | Embryonic Stem Cells | Fatty Acid Synthases | Fatty Acids | Female | Fibroblasts | HEK293 Cells | Humans | Male | Mice, Inbred C57BL | Mice, Knockout | Mice, Nude | Mice, Transgenic | Neoplasms, Experimental | Tumor Burden
Versión en línea
DOI
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