Pro-metastatic intracellular signaling of the elaidic trans fatty acid

Abstract

Trans fatty acids (TFAs) are risk factors of cardiovascular disorders, and a few studies have reported the cancer-promoting effects of TFAs. In the present study, we examined the effects and signaling of elaidic acid (EA), a TFA, in colorectal cancer (CRC) cells. Oral intake of EA increased the metastasis of CT26 mouse CRC cells by inducing the expression of stemness markers nucleostemin (NS) and CD133. Mechanisms underlying EA-induced signaling were confirmed by determining the binding of EA to G-protein coupled receptor 40 (GPR40) and GPR120 by performing surface protein internalization assay. We found that c-SRC mediated EGFR transactivation was induced by the binding of EA to GPR40 and GPR120. Moreover, EGFR signaling upregulated NS and Snail expression and downregulated E-cadherin expression in wild-type APC-containing CT26 cells, and upregulated NS, Wnt5a and CD44 expression in APC-null HT29 cells. These results indicate that EA enhances the stemness and epithelial-mesenchymal transition of CRC cells. These results also indicate the prominent metastatic potential of EA-treated cancer cells and highlight the important implications of EA on public health.

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

“…Effect of EA on cancer stem cell-proteins. Next, we examined the role of lipid rafts on the stemness of cancer cells, which is known to be enhanced by EA (5). EA treatment increased nanog production in HT29 cells; however, it was abrogated by cholesterol depletion after MbCD treatment (Fig.…”

“…We have previously reported the pro-tumoral effects of elaidic acid (EA), a major trans fatty acid (TFA) (4,5). EA is a long-chain fatty acid (LCFA) containing 18 carbon chains in a trans configuration, and is a structural isomer of oleic acid (OA).…”

“…EA promotes carcinogenesis in Min mice (6) and induces the proliferation of Ehrlich ascites sarcoma cells (7). EA enhances the metastasis of CRC in mouse models (4) by increasing cancer cell stemness and epithelial-mesenchymal transition (EMT) (5). EA also induces chemoresistance in CRC cells by upregulating its stemness (8).…”

“…EA also binds to GPR40 and 120, inducing the transactivation of EGFR via c-src (5). Lipid rafts represent a special localization of epidermal growth factor receptors (EGFRs), altering its signaling pathways (10) and transactivation (11).…”

Fatty Acids Induce Stemness in the Stromal Cells of a CT26 Mouse Tumor Model

“…TFA are associated with carcinogenesis [18][19][20] . Moreover, cancer metastasis [21,22] and drug resistance [23] are promoted by elaidic acid (EA), a major component of dietary TFA [24] , through the enhancement of stemness and epithelial-mesenchymal transition [22,23] .…”