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

International Journal of Molecular Sciences

Jing-Yuan Chuang¹  Yuan-Li Huang⁴  Wei-Lin Yen¹  I-Ping Chiang³  Ming-Hsui Tsai² 

[1] Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 402, Taiwan; E-Mails:;Department of Otolaryngology, China Medical University Hospital, Taichung 402, Taiwan; E-Mail:;Department of Pathology, China Medical University Hospital, Taichung 402, Taiwan; E-Mail:;Department of Biotechnology, College of Health Science, Asia University, Taichung 402, Taiwan; E-Mail:

关键词: Interleukin-6 (IL-6);    oral squamous cell carcinoma (OSCC);    Intercellular adhesion molecule-1 (ICAM-1);    Syk;    c-Jun N-terminal kinase (JNK);   

DOI  :  10.3390/ijms15010545

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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