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Oncotarget. 2015 Nov 17;6(36):38719-36. doi: 10.18632/oncotarget.5340.

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

Author information

1
Molecular Oncology and Nutritional Genomics of Cancer Group, IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain.
2
Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
3
Biostatistics Unit, IMDEA Food Institute, CEI UAM+CSIC, Madrid, Spain.
4
Medical Oncology, La Paz University Hospital (IdiPAZ-UAM), Madrid, Spain.
5
Precision Oncology Laboratory (POL), Infanta Sofía University Hospital, Madrid, Spain.
6
Epithelial Cell Biology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

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.

KEYWORDS:

acyl-CoA synthetases; colorectal cancer; epithelial-mesenchymal transition; lipid metabolism; stearoyl-CoA desaturase

PMID:
26451612
PMCID:
PMC4770732
DOI:
10.18632/oncotarget.5340
[Indexed for MEDLINE]
Free PMC Article

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