Journal
CELL PROLIFERATION
Volume 53, Issue 3, Pages -Publisher
WILEY
DOI: 10.1111/cpr.12776
Keywords
IL-6; metastasis; NF-kappa B; non-small-cell lung cancer; TIM-4
Categories
Funding
- Zhejiang Provincial Natural Science Foundation of China [LY18H160028]
- National Natural Science Foundation of China [81670520, 81902921]
- Taishan Scholarship [tspd20181201]
- Shandong Provincial Key Innovation project [2018YFJH0503]
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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-kappa B 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-kappa B. Conclusions TIM-4 involves in IL-6 promoted migration, invasion and EMT of NSCLC.
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