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: Ruth Sánchez-Martínez, Silvia Cruz-Gil, Marta Gómez de Cedrón, Mónica Álvarez-Fernández, Teodoro Vargas, Susana Molina, Belén García, Jesús Herranz, Juan Moreno-Rubio, Guillermo Reglero, Mirna Pérez-Moreno, Jaime Feliu, Marcos Malumbres, Ana Ramírez de Molina
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 36 Pg. 38719-36 (Nov 17 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26451612 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Stearoyl-CoA Desaturase
• Coenzyme A Ligases

Topics

• Cell Line, Tumor
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Coenzyme A Ligases (metabolism)
• Colonic Neoplasms (genetics, metabolism, pathology)
• Epithelial-Mesenchymal Transition
• HEK293 Cells
• Humans
• Lipid Metabolism
• Neoplasm Invasiveness
• Signal Transduction
• Stearoyl-CoA Desaturase (metabolism)