TY - JOUR

T1 - A link between lipid metabolism and epithelial-mesenchymal transition provides a target for colon cancer therapy

AU - Sánchez-Martínez, Ruth

AU - Cruz-Gil, Silvia

AU - Cedrón, Marta Gómez de

AU - Álvarez-Fernández, Mónica

AU - Vargas, Teodoro

AU - Molina, Susana

AU - García, Belén

AU - Herranz, Jesús

AU - Moreno-Rubio, Juan

AU - Reglero, Guillermo

AU - Perez-Moreno, Mirna

AU - Feliu, Jaime

AU - Malumbres, Marcos

AU - Molina, Ana Ramírez de

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Cell Line, Tumor

KW - Cell Movement

KW - Cell Proliferation

KW - Coenzyme A Ligases

KW - Colonic Neoplasms

KW - Epithelial-Mesenchymal Transition

KW - HEK293 Cells

KW - Humans

KW - Lipid Metabolism

KW - Neoplasm Invasiveness

KW - Signal Transduction

KW - Stearoyl-CoA Desaturase

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.18632/oncotarget.5340

DO - 10.18632/oncotarget.5340

M3 - Journal article

C2 - 26451612

VL - 6

SP - 38719

EP - 38736

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 36

ER -