2026-06-14T03:35:58Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/93172024-11-29T15:09:48Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Bueno, Maria J author Jimenez-Renard, Veronica author Samino, Sara author Capellades, Jordi author Junza, Alejandra author López-Rodríguez, María Luz author Garcia-Carceles, Javier author Lopez-Fabuel, Irene author Bolaños, Juan P author Chandel, Navdeep S author Yanes, Oscar author Colomer, Ramon author Quintela Fandino, Miguel Angel author 2019-11-01 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. Nat Commun. 2019 ;10(1):5011 10.1038/s41467-019-13028-1 2041-1723 2041-1723 Nature communications 31676791 http://hdl.handle.net/20.500.12105/9317 Essentiality of fatty acid synthase in the 2D to anchorage-independent growth transition in transforming cells