Abstract
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.
Data availability
The data that support the findings of the present study are available from the corresponding author on reasonable request.
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Acknowledgements
We thank Doctor Xu (the department of First Affiliated Hospital of China Medical University, Shenyang, China) for assistance with the donation of A549 and H1299 cells.
Funding
This study was supported by Key Projects of General Hospital of Northern Theater Command (Grant No: ZZKY2024037).
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J.M. and Y.S. designed the study. Y.S. performed the experiment; collected and analyzed the data; drafted the manuscript. H.C. and W.N. collected partial data. Y.F. C.L. A.Z. and X.L. provided the support of pathological and data. J.M. supervised the entire project, data analysis and writing of the manuscript. All authors have reviewed and approved the final manuscript.
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Shao, Y., Cheng, H., Ni, W. et al. Interleukin-7 induces EMT to promote tumor growth and metastasis in NSCLC via Notch1/TGF-β pathway. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37876-2
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DOI: https://doi.org/10.1038/s41598-026-37876-2
