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A link between lipid metabolism and epithelial-mesenchymal transition provides a target for colon cancer therapy

AuthorsSánchez-Martínez, Ruth; Vargas, Teodoro; Molina, Susana; Moreno-Rubio, Juan; Reglero, Guillermo ; Ramírez de Molina, Ana
KeywordsEpithelial-mesenchymal transition
Stearoyl-CoA desaturase
Colorectal cancer
Lipid metabolism
Acyl-coA synthetases
Issue Date2015
PublisherImpact Journals
CitationOncotarget 6(36): 38719-38736 (2015)
AbstractThe 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.
DescriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.
Publisher version (URL)https://doi.org/10.18632/oncotarget.5340
Identifiersdoi: 10.18632/oncotarget.5340
issn: 1949-2553
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