Author
Listed:
- Maria J. Bueno
(CNIO – Spanish National Cancer Research Center)
- Veronica Jimenez-Renard
(CNIO – Spanish National Cancer Research Center)
- Sara Samino
(Universitat Rovira i Virgili
CIBERDEM)
- Jordi Capellades
(Universitat Rovira i Virgili
CIBERDEM)
- Alejandra Junza
(Universitat Rovira i Virgili
CIBERDEM)
- María Luz López-Rodríguez
(Universidad Complutense)
- Javier Garcia-Carceles
(Universidad Complutense)
- Irene Lopez-Fabuel
(CSIC
Institute of Biomedical Research of Salamanca)
- Juan P. Bolaños
(CSIC
Institute of Biomedical Research of Salamanca)
- Navdeep S. Chandel
(Northwestern University Feinberg School of Medicine Chicago)
- Oscar Yanes
(Universitat Rovira i Virgili
CIBERDEM)
- Ramon Colomer
(Universitario La Princesa)
- Miguel Quintela-Fandino
(CNIO – Spanish National Cancer Research Center
Universitario Quiron
Hospital Universitario de Fuenlabrada)
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.
Suggested Citation
Maria J. Bueno & Veronica Jimenez-Renard & Sara Samino & Jordi Capellades & Alejandra Junza & María Luz López-Rodríguez & Javier Garcia-Carceles & Irene Lopez-Fabuel & Juan P. Bolaños & Navdeep S. Cha, 2019.
"Essentiality of fatty acid synthase in the 2D to anchorage-independent growth transition in transforming cells,"
Nature Communications, Nature, vol. 10(1), pages 1-18, December.
Handle:
RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13028-1
DOI: 10.1038/s41467-019-13028-1
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