Syk/JNK/AP-1 signaling pathway mediates interleukin-6-promoted cell migration in oral squamous cell carcinoma.
Syk/JNK/AP-1 signaling pathway mediates interleukin-6-promoted cell migration in oral squamous cell carcinoma.
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DOI：
10.3390/ijms15010545
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发表时间：
2014-01-06
影响因子：
5.6
通讯作者：
Tang CH
中科院分区：
文献类型：
--
作者：
Chuang JY;Huang YL;Yen WL;Chiang IP;Tsai MH;Tang CH
口腔鳞状细胞癌（OSCC）通常迁移和转移。白细胞介素-6（IL-6）是一种与疾病状态和癌症结局相关的多功能细胞因子。然而，IL-6对人OSCC细胞的作用尚不清楚。在此，我们发现IL-6增加了OSCC细胞的细胞迁移和细胞间粘附分子-1（ICAM-1）的表达。用IL-6 R单克隆抗体（mAb）预处理OSCC细胞可显著抑制IL-6诱导的细胞迁移和ICAM-1表达。相比之下，IL-6介导的细胞运动性和ICAM-1上调减弱Syk和c-Jun N-末端激酶（JNK）抑制剂。用IL-6刺激OSCC细胞促进Syk和JNK磷酸化。此外，IL-6增强AP-1活性，IL-6 R mAb、Syk抑制剂或JNK抑制剂均降低IL-6介导的c-Jun磷酸化、c-Jun与ICAM-1启动子的结合以及c-Jun向细胞核的易位。我们的研究结果表明，IL-6通过IL-6 R受体和Syk，JNK和AP-1信号转导途径增加ICAM-1的表达，增强OSCC细胞的迁移。
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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