Neuropilin 1 modulates TGF‑β1‑induced epithelial‑mesenchymal transition in non‑small cell lung cancer

Ding,Zongli; Du,Wenwen; Lei,Zhe; Zhang,Yang; Zhu,Jianjie; Zeng,Yuanyuan; Wang,Shengjie; Zheng,Yulong; Liu,Zeyi; Huang,Jian‑An

doi:10.3892/ijo.2019.4938

Neuropilin 1 modulates TGF‑β1‑induced epithelial‑mesenchymal transition in non‑small cell lung cancer

Authors:
- Zongli Ding
- Wenwen Du
- Zhe Lei
- Yang Zhang
- Jianjie Zhu
- Yuanyuan Zeng
- Shengjie Wang
- Yulong Zheng
- Zeyi Liu
- Jian‑An Huang
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Affiliations: Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Respiratory Medicine, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu 223002, P.R. China
Published online on: December 11, 2019 https://doi.org/10.3892/ijo.2019.4938
Pages: 531-543
Copyright: © Ding et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previously, the authors reported that neuropilin‑1 (NRP1) was significantly increased and acted as a vital promoter in the metastasis of non‑small cell lung cancer (NSCLC). However, the regulatory mechanism of NRP1 in NSCLC cell migration and invasion remained unclear. The present study aimed to explore the regulatory mechanism of NRP1 in the transforming growth factor‑β (TGF‑β) 1‑induced migration and invasion of NSCLC cells. The expression level of NRP1 was determined by RT‑qPCR analysis in human tissue samples with or without lymph node metastasis. Transwell assay and wound healing assay were conducted to determine the cell migration. Lentivirus‑mediated stable knockdown and overexpression of NRP1 cell lines were constructed. Exogenous TGF‑β1 stimulation, SIS3 treatment, western blot analysis and in vivo metastatic model were utilized to clarify the underlying regulatory mechanisms. The results demonstrated that the expression of NRP1 was increased in metastatic NSCLC tissues. NRP1 promoted NSCLC metastasis in vitro and in vivo. The Transwell assays, wound healing assays and western blot analysis revealed that the knockdown of NRP1 significantly inhibited TGF‑β1‑mediated EMT and migratory and invasive capabilities of NSCLC. Furthermore, the overexpression of NRP1 weakened the inhibitory effect of SIS3 on the NSCLC migration and invasion. Co‑IP assay revealed that NRP1 interacted with TGFβRII to induce EMT. On the whole, the findings of this study demonstrated that NRP1 was overexpressed in metastatic NSCLC tissues. NRP1 could contributes to TGF‑β1‑induced EMT and metastasis in NSCLC by binding with TGFβRII.

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