2026-06-14T03:32:15Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/93172024-11-29T15:09:48Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
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
funder
Instituto de Salud Carlos III
funder
Unión Europea
funder
Asociación Española Contra el Cáncer
funder
United States Department of Health and Human Services
funder
Ministerio de Economía y Competitividad (España)
funder
Junta de Castilla y León (España)
funder
Fundación BBVA
funder
Fundación Ramón Areces
2020-03-24T18:31:59Z
2020-03-24T18:31:59Z
2019-11-01
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
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.
eng
Essentiality of fatty acid synthase in the 2D to anchorage-independent growth transition in transforming cells
journal article
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