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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anthracenes / pharmacology
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Antibodies, Monoclonal / immunology
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Carcinoma, Squamous Cell / metabolism
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Carcinoma, Squamous Cell / pathology
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Cell Line, Tumor
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Cell Movement / drug effects*
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Humans
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Intercellular Adhesion Molecule-1 / chemistry
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / metabolism
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Interleukin-6 / antagonists & inhibitors
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Interleukin-6 / genetics
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Interleukin-6 / pharmacology*
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JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
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JNK Mitogen-Activated Protein Kinases / metabolism*
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Mouth Neoplasms / metabolism
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Mouth Neoplasms / pathology
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Phosphorylation / drug effects
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RNA Interference
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RNA, Small Interfering / metabolism
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Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
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Receptor Protein-Tyrosine Kinases / metabolism*
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Receptors, Interleukin-6 / immunology
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Receptors, Interleukin-6 / metabolism
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Signal Transduction / drug effects
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Transcription Factor AP-1 / metabolism*
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Up-Regulation / drug effects
Substances
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Anthracenes
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Antibodies, Monoclonal
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Interleukin-6
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RNA, Small Interfering
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Receptors, Interleukin-6
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Transcription Factor AP-1
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Intercellular Adhesion Molecule-1
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pyrazolanthrone
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Receptor Protein-Tyrosine Kinases
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TYRO3 protein, human
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JNK Mitogen-Activated Protein Kinases