title: 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.
authors.affiliation: Department of Molecular Pathology, Nara Medical University, Kashihara 634-8521, Japan.
authors.forename: Kiyomu
authors.initials: K
authors.lastname: Fujii
authors.affiliation: Department of Molecular Pathology, Nara Medical University, Kashihara 634-8521, Japan.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Molecular Pathology, Nara Medical University, Kashihara 634-8521, Japan.
authors.forename: Rina
authors.initials: R
authors.lastname: Fujiwara-Tani
authors.affiliation: Department of Molecular Pathology, Nara Medical University, Kashihara 634-8521, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kishi
authors.affiliation: Department of Pathology, Nantong University Cancer Hospital, Nantong, Jiangsu 226361, P.R. China.
authors.forename: Song
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Pathology, Nantong University Cancer Hospital, Nantong, Jiangsu 226361, P.R. China.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Gastroenterological Surgery, Fukuoka University School of Medicine, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of Molecular Pathology, Nara Medical University, Kashihara 634-8521, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohmori
authors.affiliation: Department of Molecular Pathology, Nara Medical University, Kashihara 634-8521, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
mesh_terms: D000818:Animals; D015820:Cadherins / Q000096:biosynthesis; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D066246:ErbB Receptors / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D019301:Oleic Acid / Q000008:administration & dosage*; D009829:Oleic Acids; D015398:Signal Transduction / Q000187:drug effects; D044242:Trans Fatty Acids / Q000008:administration & dosage*; D015533:Transcriptional Activation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D015820:Cadherins; D009829:Oleic Acids; D044242:Trans Fatty Acids; D019301:Oleic Acid; C011459:elaidic acid; C512478:EGFR protein, human; D066246:ErbB Receptors