title: Chemical genomic-based pathway analyses for epidermal growth factor-mediated signaling in migrating cancer cells.
abstract: To explore the diversity and consistency of the signaling pathways that regulate tumor cell migration, we chose three human tumor cell lines that migrated after treatment with EGF. We then quantified the effect of fifteen inhibitors on the levels of expression or the phosphorylation levels of nine proteins that were induced by EGF stimulation in each of these cell lines. Based on the data obtained in this study and chemical-biological assumptions, we deduced cell migration pathways in each tumor cell line, and then compared them. As a result, we found that both the MEK/ERK and JNK/c-Jun pathways were activated in all three migrating cell lines. Moreover, GSK-3 and p38 were found to regulate PI3K/Akt pathway in only EC109 cells, and JNK was found to crosstalk with p38 and Fos related pathway in only TT cells. Taken together, our analytical system could easily distinguish between the common and cell type-specific pathways responsible for tumor cell migration.
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Magi
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Saeki
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kasamatsu
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa Japan.
authors.forename: Etsu
authors.initials: E
authors.lastname: Tashiro
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Imoto
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D004815:Epidermal Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3