Contribution of the & alpha;5 nAChR Subunit and & alpha;5SNP to Nicotine-Induced Proliferation and Migration of Human Cancer Cells

Nicotine in tobacco is known to induce tumor-promoting effects and cause chemotherapy resistance through the activation of nicotinic acetylcholine receptors (nAChRs). Many studies have associated the a5 nicotinic receptor subunit (a5), and a specific polymorphism in this subunit, with (i) nicotine administration, (ii) nicotine dependence, and (iii) lung cancer. The a5 gene CHRNA5 mRNA is upregulated in several types of cancer, including lung, prostate, colorectal, and stomach cancer, and cancer severity is correlated with smoking. In this study, we investigate the contribution of a5 in the nicotine-induced cancer hallmark functions proliferation and migration, in breast, colon, and prostate cancer cells. Nine human cell lines from different origins were used to determine nAChR subunit expression levels. Then, selected breast (MCF7), colon (SW480), and prostate (DU145) cancer cell lines were used to investigate the nicotine-induced effects mediated by a5. Using pharmacological and siRNA-based experiments, we show that a5 is essential for nicotine-induced proliferation and migration. Additionally, upon downregulation of a5, nicotine-promoted expression of EMT markers and immune regulatory proteins was impaired. Moreover, the a5 polymorphism D398N (a5SNP) caused a basal increase in proliferation and migration in the DU145 cell line, and the effect was mediated through G-protein signaling. Taken together, our results indicate that nicotine-induced cancer cell proliferation and migration are mediated via a5, adding to the characterization of a5 as a putative therapeutical target.

Automated summary

Nicotine in tobacco induces tumor-promoting effects and chemotherapy resistance through nicotinic acetylcholine receptors (nAChRs). This study investigates the role of a5 subunit in nicotine-induced cancer cell proliferation and migration in breast, colon, and prostate cancer cells. The results show that nicotine-induced proliferation and migration are mediated by a5.