IL‐6 promotes metastasis of non‐small‐cell lung cancer by up‐regulating TIM‐4 via NF‐κB

作者：Wen Liu, Hongxing Wang, Fuxiang Bai, Lu Ding, Yanyan Huang, Changchang Lu, Siyuan Chen, Chunyang Li, Xuetian Yue, Xiaohong Liang, Chunhong Ma, Liyun Xu, Lifen Gao · 发表于：Cell Proliferation · 年份：2020 · DOI：10.1111/cpr.12776 · 被引用次数：142 · 研究领域：Galectins and Cancer Biology、Glycosylation and Glycoproteins Research、Studies on Chitinases and Chitosanases

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.