标题：IL-6 promotes metastasis of non-small-cell lung cancer by up-regulating TIM-4 via NF-κB
作者：Liu W.; Wang H.; Bai F.; Ding L.; Huang Y.; Lu C.; Chen S.; Li C.;等 更多 作者机构：[Liu, W] Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, Shandong Provincial Key Laboratory of Infec 更多
通讯作者地址：[Xu, L] Cell and Molecular Biology Laboratory, Zhoushan HospitalChina;
关键词：IL-6; metastasis; NF-κB; non-small-cell lung cancer; TIM-4
摘要：Objectives: Interleukin-6 (IL-6) is critical for the development of non-small-cell lung cancer (NSCLC). Recently, we identified T-cell immunoglobulin domain and mucin domain 4 (TIM-4) as a new pro-growth player in NSCLC progression. However, the role of TIM-4 in IL-6-promoted NSCLC migration, invasion and epithelial-to-mesenchymal transition (EMT) remains unclear. Materials and Methods: Expressions of TIM-4 and IL-6 were both evaluated by immunohistochemical staining in NSCLC tissues. Real-time quantitative PCR (qPCR), Western blot, flow cytometry and RT-PCR were performed to detect TIM-4 expression in NSCLC cells with IL-6 stimulation. The roles of TIM-4 in IL-6 promoting migration and invasion of NSCLC were detected by transwell assay. EMT-related markers were analysed by qPCR and Western blot in vitro, and metastasis was evaluated in BALB/c nude mice using lung cancer metastasis mouse model in vivo. Results: High IL-6 expression was identified as an independent predictive factor for TIM-4 expression in NSCLC tissues. NSCLC patients with TIM-4 and IL-6 double high expression showed the worst prognosis. IL-6 promoted TIM-4 expression in NSCLC cells depending on NF-κB signal pathway. Both TIM-4 and IL-6 promoted migration, invasion and EMT of NSCLC cells. Interestingly, TIM-4 knockdown reversed the role of IL-6 in NSCLC and IL-6 promoted metastasis of NSCLC by up-regulating TIM-4 via NF-κB. Conclusions: TIM-4 involves in IL-6 promoted migration, invasion and EMT of NSCLC. © 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.