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.
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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.
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. International Journal of Molecular Sciences. 2014; 15(1):545-559.
Chuang, Jing-Yuan; Huang, Yuan-Li; Yen, Wei-Lin; Chiang, I-Ping; Tsai, Ming-Hsui; Tang, Chih-Hsin. 2014. "Syk/JNK/AP-1 Signaling Pathway Mediates Interleukin-6-Promoted Cell Migration in Oral Squamous Cell Carcinoma." Int. J. Mol. Sci. 15, no. 1: 545-559.