Essentiality of fatty acid synthase in the 2D to anchorage-independent growth transition in transforming cells.
Nat Commun
; 10(1): 5011, 2019 11 01.
Article
en En
| MEDLINE
| ID: mdl-31676791
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células Madre Embrionarias
/
Ácido Graso Sintasas
/
Ácidos Grasos
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Fibroblastos
/
Neoplasias Experimentales
Límite:
Animals
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Female
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Humans
/
Male
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
España