Interleukin-7 induces EMT to promote tumor growth and metastasis in NSCLC via Notch1/TGF-β pathway.

Interleukin 7 (IL‑7) regulates lymphangiogenesis and proliferation, inhibits apoptosis and autophagy in non‑small cell lung cancer (NSCLC). However, the role and detailed molecular mechanism of IL‑7 involved in NSCLC epithelial-to-mesenchymal transition (EMT) remain unknown. In this study, 119 cases of NSCLC tissue specimens were used to determine the expression levels and prognostic values of IL-7, IL-7R, E-cadherin and Vimentin. The CCK8, wound healing and transwell migration and invasion assays were employed to detect the NSCLC cell proliferation, migration and invasion, respectively. A subcutaneous tumor model and tail vein tumor injection in C57BL/6J mice were used to assess the role of IL-7 in vivo. Western blot, qRT-PCR and phalloidin staining assays were performed to investigate the molecular functions of IL-7. We find that IL‑7 down‑regulates E-cadherin, then up‑regulates N-cadherin, Vimentin and Snail1. In addition, IL-7 induces the expression of protein and mRNA of Notch1 and TGF-β. Inhibition of Notch1/TGF-β pathway reverses the proliferation, migration, invasiveness and EMT transition in NSCLC. In vivo, we find IL-7 promotes the growth of tumor and increases the number of lung metastasis nodules. E-cadherin is correlated with patients' survival and IL-7R is the strongest predictor of survival. In conclusion, IL-7 induces EMT to promote growth and metastasis NSCLC via the activation of Notch1/TGF-β pathway. IL-7 may be a potential target against human NSCLC.