Oncotarget

Research Papers:

Role of α7-nicotinic acetylcholine receptor in nicotine-induced invasion and epithelial-to-mesenchymal transition in human non-small cell lung cancer cells

Chun Zhang, Xu-Ping Ding, Qing-Nan Zhao, Xin-Jie Yang, Shi-Min An, Hao Wang, Lu Xu, Liang Zhu _ and Hong-Zhuan Chen

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Oncotarget. 2016; 7:59199-59208. https://doi.org/10.18632/oncotarget.10498

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Abstract

Chun Zhang1,2,*, Xu-Ping Ding1,*, Qing-Nan Zhao1,*, Xin-Jie Yang1, Shi-Min An1, Hao Wang1, Lu Xu1, Liang Zhu1, Hong-Zhuan Chen1

1Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

2Department of Pharmacy, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China

*These authors have contributed equally to this work

Correspondence to:

Liang Zhu, email: jyzhul@shsmu.edu.cn

Lu Xu, email: luxuluxu@yahoo.com

Hong-Zhuan Chen, email: hongzhuan_chen@hotmail.com

Keywords: α7-nAChR, nicotine, invasion, EMT, NSCLC

Received: October 20, 2015     Accepted: June 29, 2016     Published: July 08, 2016

ABSTRACT

Nicotine via nicotinic acetylcholine receptors (nAChRs) stimulates non-small cell lung cancer (NSCLC) cell invasion and epithelial to mesenchymal transition (EMT) which underpin the cancer metastasis. However, the receptor subtype-dependent effects of nAChRs on NSCLC cell invasion and EMT, and the signaling pathway underlying the effects remain not fully defined. We identified that nicotine induced NSCLC cell invasion, migration, and EMT; the effects were suppressed by pharmacological intervention using α7-nAChR selective antagonists or by genetic intervention using α7-nAChR knockdown via RNA inference. Meanwhile, nicotine induced activation of MEK/ERK signaling in NSCLC cells; α7-nAChR antagonism or MEK/ERK signaling pathway inhibition suppressed NSCLC cell invasion and EMT marker expression. These results indicate that nicotine induces NSCLC cell invasion, migration, and EMT; the effects are mediated by α7-nAChRs and involve MEK/ERK signaling pathway. Delineating the effect of nicotine on the NSCLC cell invasion and EMT at receptor subtype level would improve the understanding of cancer biology and offer potentials for the exploitation of selective ligands for the control of the cancer metastasis.


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