A link between lipid metabolism and epithelial-mesenchymal transition provides a target for colon cancer therapy
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Ruth Sánchez-Martínez1, Silvia Cruz-Gil1,*, Marta Gómez de Cedrón1,*, Mónica Álvarez-Fernández2, Teodoro Vargas1, Susana Molina1, Belén García1, Jesús Herranz3, Juan Moreno-Rubio4,5, Guillermo Reglero1, Mirna Pérez-Moreno6, Jaime Feliu4, Marcos Malumbres2, Ana Ramírez de Molina1
1Molecular Oncology and Nutritional Genomics of Cancer Group, IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain
2Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
3Biostatistics Unit, IMDEA Food Institute, CEI UAM+CSIC, Madrid, Spain
4Medical Oncology, La Paz University Hospital (IdiPAZ-UAM), Madrid, Spain
5Precision Oncology Laboratory (POL), Infanta Sofía University Hospital, Madrid, Spain
6Epithelial Cell Biology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
*These authors have contributed equally to this work
Ana Ramírez de Molina, e-mail: firstname.lastname@example.org
Keywords: colorectal cancer, lipid metabolism, acyl-CoA synthetases, stearoyl-CoA desaturase, epithelial-mesenchymal transition
Received: June 08, 2015 Accepted: September 24, 2015 Published: October 05, 2015
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.
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