α5-nAChR modulates nicotine-induced cell migration and invasion in A549 lung cancer cells

Cigarette smoking is the most important risk factor in the development of human lung cancer. Nicotine, the major component in tobacco, not only contributes to carcinogenesis but also promotes tumor metastasis. By binding to nicotinic acetylcholine receptors (nAChRs), nicotine induces the proliferation and migration of non-small cell lung cancer. Recently studies have indicated that alpha 5-nAChR is highly associated with lung cancer risk and nicotine dependence. Nevertheless, it is unclear whether nicotine promotes the migration and invasion through activation of alpha 5-nAChR in lung cancer. In the present study, A549 cell was exposed to 1 mu N nicotine for 8, 24 or 48 h. Wound-healing assay and transwell assay were used to evaluate the capability of A549 cell migration and cell invasion, respectively. Silencing of alpha 5-nAChR was done by siRNA. Western blotting and PCR were used to detect alpha 5-nAChR expression. Nicotine can induce activation of alpha 5-nAChR in association with increased migration and invasion of human lung cancer A549 cell. Treatment of cells with alpha 5-nAChR specific siRNA blocks nicotine-stimulated activation of alpha 5-nAChR and suppresses A549 cell migration and invasion. Reduction of alpha 5-nAChR resulted in upregulation of E-cadherin, consistent with E-cadherin being inhibitive of cancer cell invasion. These findings suggest that nicotine-induced migration and invasion may occur in a mechanism through activation of alpha 5-nAChR, which can contribute to metastasis or development of human lung cancer. (C) 2015 Elsevier GmbH. All rights reserved.