Author, as appears in the article.: Bueno, Maria J; Jimenez-Renard, Veronica; Samino, Sara; Capellades, Jordi; Junza, Alejandra; Luz Lopez-Rodriguez, Maria; Garcia-Carceles, Javier; Lopez-Fabuel, Irene; Bolanos, Juan P; Chandel, Navdeep S; Yanes, Oscar; Colomer, Ramon; Quintela-Fandino, Miguel
Department: Enginyeria Electrònica, Elèctrica i Automàtica
URV's Author/s: Junza Martínez, Alexandra / SAMINO GENÉ, SARA / Yanes Torrado, Óscar
Keywords: Tumor burden Suppresses Overexpression Orlistat Oncogene Neoplasms, experimental Mice, transgenic Mice, nude Mice, knockout Mice, inbred c57bl Male Inhibition Humans Hek293 cells Glucose-metabolism Fibroblasts Female Fatty acids Fatty acid synthases Expression Embryonic stem cells Embryo, mammalian Cells, cultured Cell line Carboxylase Cancer Animals Activates ppar-alpha
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.
Thematic Areas: Zootecnia / recursos pesqueiros Saúde coletiva Química Psicología Planejamento urbano e regional / demografia Physics and astronomy (miscellaneous) Physics and astronomy (all) Odontología Nutrição Multidisciplinary sciences Multidisciplinary Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Matemática / probabilidade e estatística Interdisciplinar Geociências General physics and astronomy General medicine General chemistry General biochemistry,genetics and molecular biology Farmacia Engenharias iv Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência da computação Chemistry (miscellaneous) Chemistry (all) Biotecnología Biodiversidade Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all) Astronomia / física Antropologia / arqueologia
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 20411723
Author's mail: oscar.yanes@urv.cat alexandra.junza@urv.cat
Author identifier: 0000-0003-3695-7157 0000-0001-7205-0419
Record's date: 2024-10-12
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.nature.com/articles/s41467-019-13028-1
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Nature Communications. 10 (5011): 5011-
APA: Bueno, Maria J; Jimenez-Renard, Veronica; Samino, Sara; Capellades, Jordi; Junza, Alejandra; Luz Lopez-Rodriguez, Maria; Garcia-Carceles, Javier; Lope (2019). Essentiality of fatty acid synthase in the 2D to anchorage-independent growth transition in transforming cells. Nature Communications, 10(5011), 5011-. DOI: 10.1038/s41467-019-13028-1
Article's DOI: 10.1038/s41467-019-13028-1
Entity: Universitat Rovira i Virgili
Journal publication year: 2019
Publication Type: Journal Publications
Repositori URV