title: A link between lipid metabolism and epithelial-mesenchymal transition provides a target for colon cancer therapy.
abstract: The alterations in carbohydrate metabolism that fuel tumor growth have been extensively studied. However, other metabolic pathways involved in malignant progression, demand further understanding. Here we describe a metabolic acyl-CoA synthetase/stearoyl-CoA desaturase ACSL/SCD network causing an epithelial-mesenchymal transition (EMT) program that promotes migration and invasion of colon cancer cells. The mesenchymal phenotype produced upon overexpression of these enzymes is reverted through reactivation of AMPK signaling. Furthermore, this network expression correlates with poorer clinical outcome of stage-II colon cancer patients. Finally, combined treatment with chemical inhibitors of ACSL/SCD selectively decreases cancer cell viability without reducing normal cells viability. Thus, ACSL/SCD network stimulates colon cancer progression through conferring increased energetic capacity and invasive and migratory properties to cancer cells, and might represent a new therapeutic opportunity for colon cancer treatment.
authors.affiliation: Molecular Oncology and Nutritional Genomics of Cancer Group, IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain.
authors.forename: Ruth
authors.initials: R
authors.lastname: Sánchez-Martínez
authors.affiliation: Molecular Oncology and Nutritional Genomics of Cancer Group, IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cruz-Gil
authors.affiliation: Molecular Oncology and Nutritional Genomics of Cancer Group, IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Gómez de Cedrón
authors.affiliation: Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Álvarez-Fernández
authors.affiliation: Molecular Oncology and Nutritional Genomics of Cancer Group, IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain.
authors.forename: Teodoro
authors.initials: T
authors.lastname: Vargas
authors.affiliation: Molecular Oncology and Nutritional Genomics of Cancer Group, IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Molina
authors.affiliation: Molecular Oncology and Nutritional Genomics of Cancer Group, IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: García
authors.affiliation: Biostatistics Unit, IMDEA Food Institute, CEI UAM+CSIC, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Herranz
authors.affiliation: Medical Oncology, La Paz University Hospital (IdiPAZ-UAM), Madrid, Spain.|Precision Oncology Laboratory (POL), Infanta Sofía University Hospital, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Moreno-Rubio
authors.affiliation: Molecular Oncology and Nutritional Genomics of Cancer Group, IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Reglero
authors.affiliation: Epithelial Cell Biology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Mirna
authors.initials: M
authors.lastname: Pérez-Moreno
authors.affiliation: Medical Oncology, La Paz University Hospital (IdiPAZ-UAM), Madrid, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Feliu
authors.affiliation: Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Malumbres
authors.affiliation: Molecular Oncology and Nutritional Genomics of Cancer Group, IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ramírez de Molina
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D003066:Coenzyme A Ligases / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D057809:HEK293 Cells; D006801:Humans; D050356:Lipid Metabolism; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism
chemical_list: D013230:Stearoyl-CoA Desaturase; D003066:Coenzyme A Ligases
keywords: acyl-CoA synthetases; colorectal cancer; epithelial-mesenchymal transition; lipid metabolism; stearoyl-CoA desaturase