期刊
ONCOTARGET
卷 6, 期 36, 页码 38719-38736出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.5340
关键词
colorectal cancer; lipid metabolism; acyl-CoA synthetases; stearoyl-CoA desaturase; epithelial-mesenchymal transition
资金
- Ministerio de Economia y Competitividad del Gobierno de Espana (MINECO, Plan Nacional I+D+i) [AGL2013-48943-C2]
- Gobierno regional de la Comunidad de Madrid [P2013/ABI-2728]
- EU Structural Funds
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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