Abstract 1032: The acetylcholine signaling pathway: A novel molecular target for lung cancers

Abstract

Abstract Cigarette smoking is a major risk factor for all types of lung cancers. Nicotine, the addictive component of cigarettes, accelerates the growth and angiogenesis of human lung cancers. The biological activity of nicotine is mediated by nicotinic acetylcholine receptors (nAChRs). The endogenous ligand of nAChRs is acetylcholine (ACh). We show that both human SCLCs and NSCLCs contain all proteins of the acetylcholine signaling pathway, namely nAChRs, choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), choline transporter (ChT1) and acetylcholinesterase (AChE). ACh functions as an autocrine growth factor for human lung cancer cells. Lung adenocarcinoma (LAC), squamous cell carcinoma (SCC-L) and invasive mucinous adenocarcinoma (IMA) express a diverse array of nAChRs. In addition, normal human lung cells also express nAChRs and other ACh signaling proteins. Nicotine amplifies the ACh signaling loop in human lung cancer cells. It increases the levels of alpha7-nAChR subunit in human SCC-Ls. The alpha7-nAChR is responsible for the proliferative and pro-angiogenic activity of nicotine in lung cancer. The level of alpha7-nAChR was analyzed in human SCC-L samples isolated from patients. It was found that the level of alpha7-nAChR in SCC-L patients (who are heavy smokers) was much higher than that of moderate smoker suffering from SCC-Ls. Nicotine was also found to elevate the levels of ChAT and VAChT in human lung cancers. The acetylcholine signaling pathway may be a useful molecular target for the diagnosis and therapy of human lung cancers in smokers. Our results are also relevant to lung cancer patients who are exposed to nicotine via secondhand smoke, nicotine patches, gums or electronic cigarettes. Citation Format: Kathleen C. Brown, Jamie K. Lau, Haley E. Perry, Brent A. Thornhill, Cathryn D. Stevenson, William D. Rollyson, Cody A. Stover, Dennie V. Jones, Joseph F. Pulliam, Piyali Dasgupta. The acetylcholine signaling pathway: A novel molecular target for lung cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1032. doi:10.1158/1538-7445.AM2015-1032