论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
在非小细胞肺癌中,HGF/MET 通过 FOSL2 调节上皮-间质转化和转移
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
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