title: Syk/JNK/AP-1 signaling pathway mediates interleukin-6-promoted cell migration in oral squamous cell carcinoma.
abstract: Oral squamous cell carcinoma (OSCC) typically migrates and metastasizes. Interleukin-6 (IL-6) is a multifunctional cytokine associated with disease status and cancer outcomes. The effect of IL-6 on human OSCC cells, however, is unknown. Here, we showed that IL-6 increased cell migration and Intercellular adhesion molecule-1 (ICAM-1) expression in OSCC cells. Pretreatment of OSCC cells with IL-6R monoclonal antibody (mAb) significantly abolished IL-6-induced cell migration and ICAM-1 expression. By contrast, IL-6-mediated cell motility and ICAM-1 upregulation were attenuated by the Syk and c-Jun N-terminal kinase (JNK) inhibitors. Stimulation of OSCC cells with IL-6 promoted Syk and JNK phosphorylation. Furthermore, IL-6 enhanced AP-1 activity, and the IL-6R mAb, Syk inhibitor, or JNK inhibitor all reduced IL-6-mediated c-Jun phosphorylation, c-Jun binding to the ICAM-1 promoter, and c-Jun translocation into the nucleus. Our results indicate that IL-6 enhances the migration of OSCC cells by increasing ICAM-1 expression through the IL-6R receptor and the Syk, JNK, and AP-1 signal transduction pathways.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 402, Taiwan. alise9042@yahoo.com.tw.
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Chuang
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 402, Taiwan. yuanli@asia.edu.tw.
authors.forename: Yuan-Li
authors.initials: YL
authors.lastname: Huang
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 402, Taiwan. wielin@pchome.com.tw.
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Yen
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 402, Taiwan. d6868@mail.cmuh.org.tw.
authors.forename: I-Ping
authors.initials: IP
authors.lastname: Chiang
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 402, Taiwan. minghsui@mail.cmuh.org.tw.
authors.forename: Ming-Hsui
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 402, Taiwan. chtang@mail.cmu.edu.tw.
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
chemical_list: D000873:Anthracenes; D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1; D015850:Interleukin-6; D048031:JNK Mitogen-Activated Protein Kinases; D034741:RNA, Small Interfering; D020794:Receptor Protein-Tyrosine Kinases; D019947:Receptors, Interleukin-6; D018808:Transcription Factor AP-1; D000093242:Interleukin-6 Inhibitors; C432165:pyrazolanthrone; C084944:TYRO3 protein, human