Recent studies have showed that α5 nicotinic acetylcholine receptor (α5-nAChR) is closely associated with nicotine-related lung cancer. Our previous studies also demonstrated that α5-nAChR mediates nicotine-induced lung carcinogenesis. However, the mechanism by which α5-nAChR functions in lung carcinogenesis remains to be elucidated. Jab1/Csn5 is a key regulatory factor in smoking-induced lung cancer. In this study, we explored the underlying mechanisms linking the α5-nAChR-Jab1/Csn5 axis with lung cancer epithelial-mesenchymal transition (EMT) and metastasis, which may provide potential therapeutic targets for future lung cancer treatments. Our results demonstrated that the expression of α5-nAChR was correlated with the expression of Jab1/Csn5 in lung cancer tissues and lung cancer cells. α5-nAChR expression is associated with Jab1/Csn5 expression in lung tumour xenografts in mice. In vitro, the expression of α5-nAChR mediated Stat3 and Jab1/Csn5 expression, significantly regulating the expression of the EMT markers, N-cadherin and Vimentin. In addition, the down-regulation of α5-nAChR or/and Stat3 reduced Jab1/Csn5 expression, while the silencing of α5-nAChR or Jab1/Csn5 inhibited the migration and invasion of NSCLC cells. Mechanistically, α5-nAChR contributes to EMT and metastasis by regulating Stat3-Jab1/Csn5 signalling in NSCLC, suggesting that α5-nAChR may be a potential target in NSCLC diagnosis and immunotherapy.
Keywords: Jab1/Csn5; epithelial-mesenchymal transition; non-small-cell lung cancer; α5-nicotinic acetylcholine receptor.
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.