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Int. J. Mol. Sci. 2014, 15(1), 545-559; doi:10.3390/ijms15010545
Article

Syk/JNK/AP-1 Signaling Pathway Mediates Interleukin-6-Promoted Cell Migration in Oral Squamous Cell Carcinoma

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Received: 5 November 2013 / Revised: 20 December 2013 / Accepted: 23 December 2013 / Published: 6 January 2014
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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.
Keywords: Interleukin-6 (IL-6); oral squamous cell carcinoma (OSCC); Intercellular adhesion molecule-1 (ICAM-1); Syk; c-Jun N-terminal kinase (JNK) Interleukin-6 (IL-6); oral squamous cell carcinoma (OSCC); Intercellular adhesion molecule-1 (ICAM-1); Syk; c-Jun N-terminal kinase (JNK)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Chuang, J.-Y.; Huang, Y.-L.; Yen, W.-L.; Chiang, I.-P.; Tsai, M.-H.; Tang, C.-H. Syk/JNK/AP-1 Signaling Pathway Mediates Interleukin-6-Promoted Cell Migration in Oral Squamous Cell Carcinoma. Int. J. Mol. Sci. 2014, 15, 545-559.

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