Pro-metastatic signaling of the trans fatty acid elaidic acid is associated with lipid rafts

Abstract

Trans fatty acids (TFAs) are risk factors for cardiovascular disorders, and the cancer-promoting effects of TFAs have been previously reported. The present study examined the effects and signaling of elaidic acid (EA), a TFA, in colorectal cancer (CRC) cells. Oral intake of EA was found to increase metastasis of HT29 human CRC cells. Results indicated that, in the plasma membrane, EA was integrated into cholesterol rafts, which contain epidermal growth factor receptors (EGFR). EA increased nanog and c-myc, and decreased PGC-1A through lipid raft-associated EGFR signaling in HT29 cells. Depletion of cholesterol by methyl-β-cyclodextrin treatment abrogated the EA-induced stemness and oxidative phosphorylation. Simvastatin treatment also abrogated EA-enhanced tumor growth. These results indicate that EA enhances the stemness by activating EGFR in lipid rafts.