The roles of nicotinic acetylcholine receptor alpha 7 in mediating effects of smoking in lung cancer

Abstract

Lung cancer is the leading cause of cancer mortality worldwide. Adenocarcinoma (AD) is the most common histological subtype of non-small cell lung cancer (NSCLC). Tobacco use is the most prominent risk factor for development of lung cancer. Nicotinic acetylcholine receptor alpha 7 (nAChR α7) has been shown to play crucial roles in multiple biological processes which are important in tumorigenesis, including cell growth, cell survival, cell migration and angiogenesis, aggravated by cigarette smoke exposure.

In the first part of this study, in vitro experiments identified lung cancer cell proliferation and migration were enhanced and chemo-sensitivity remained unchanged after cigarette smoke extract (CSE) exposure. Furthermore, CSE exposure in some lung AD cell lines resulted in increased expression of nAChR α7 and increased phosphorylation of ERK and Akt, but E-cadherin expression found to be reduced.

In the second part, in vitro silencing of nAChR α7 by specific siRNA altered the levels of cell proliferation and migration in response to CSE. The expression levels of ERK, Akt and E-cadherin protein appeared to be modulated by nAChR α7 when knockdown of nAChR α7 with CSE exposure tended to induce tumor cell proliferation and migration.

In the third part, the protein expression levels of nAChR α7 in primary lung AD samples were assessed. The expression of nAChR α7 showed no association with clinical parameters including age, gender, smoking status, pathological stages and EGFR mutation status. Furthermore, the protein level of nAChR α7 was found not to be an independent predictor for progression free survival (DFS) and overall survival (OS) in patients with resected pulmonary AD.

In summary, in vitro experiments in this study suggested that nAChR α7 expression could promote cell proliferation and migration in lung cancer via the E-cadherin, ERK and Akt pathways, especially in smoking-related lung cancer. nAChR α7 protein expression was not an independent and significant prognostic factor for DFS and OS in resected lung AD patients.