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

• Main Authors: Yin J, Hu W, Fu W, Dai L, Jiang Z, Zhong S, Deng B, Zhao J
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-11-01
• Series: OncoTargets and Therapy
• Subjects: non-small cell lung cancer; metastasis; hgf/met; fosl2; snai2
• Online Access: https://www.dovepress.com/hgfmet-regulated-epithelial-mesenchymal-transitions-and-metastasis-by--peer-reviewed-article-OTT

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 workCorrespondence: Jian ZhaoDepartment of Chest Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong 510095, People’s Republic of ChinaEmail [e-mail]: 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