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HGF/MET Regulated Epithelial-Mesenchymal Transitions And Metastasis By FOSL2 In Non-Small Cell Lung Cancer

Authors Yin J, Hu W, Fu W, Dai L, Jiang Z, Zhong S, Deng B, Zhao J

Received 29 May 2019

Accepted for publication 17 September 2019

Published 5 November 2019 Volume 2019:12 Pages 9227—9237

DOI https://doi.org/10.2147/OTT.S217595

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Rachel Predeepa

Peer reviewer comments 2

Editor who approved publication: Dr Federico Perche


Jun Yin,1,* Weimin Hu,2,* Wenfan Fu,1 Lu Dai,1 Zeyong Jiang,1 Shengpeng Zhong,1 Boyun Deng,1 Jian Zhao1

1Department of Chest Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong 510095, People’s Republic of China; 2Department of Abdominal Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong 510095, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jian Zhao
Department of Chest Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong 510095, People’s Republic of China
Email tottijun@163.com

Background: HGF/MET has been found to be associated with non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms of HGF/MET involved in regulating the metastasis of NSCLC remain unclear.
Methods: The effect of HGF/MET and FOSL2 on cell migration and invasion were assessed by transwell and scratch assays. HGF/MET-induced phosphorylation and upregulation of FOSL2 was analyzed by RT-PCR and Western blotting. Regulatory effects of FOSL2 on SNAI2 transcription were detected by chromatin immunoprecipitation (ChIP) and dual-Luciferase reporter assays. The correlations of FOSL2 expression with clinical outcomes were assessed in 56 NSCLC patients.
Results: HGF/MET induced the phosphorylation and upregulation of FOSL2 by ERK1/2 kinase, FOSL2 promoted the transcription of SNAI2 by binding with the SNAI2 promoter, and SNAI2 subsequently promoted the epithelial-mesenchymal transition (EMT), invasion, and migration of NSCLC cells. According to the clinical correlation analysis in NSCLC, high expression of FOSL2 correlated with advanced tumor stage and metastasis.
Conclusion: Our studies propose that the regulatory mechanisms of the HGF/MET-induced cascade pathway is mediated by FOSL2 in NSCLC metastasis and suggested that FOSL2 could potentially be employed as a prognostic biomarker and potential therapeutic target of NSCLC metastasis.

Keywords: non-small cell lung cancer, metastasis, HGF/MET, FOSL2, SNAI2


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