Nicotinic receptor and tobacco-related cancer

Currently, tobacco smoking causes approximately 5–6 million deaths per year including more than 35% of all cancer deaths. Nicotine, the addictive constituent of tobacco, and its derived carcinogenic nitrosamines, contribute to cancer promotion and progression through the activation of nicotinic acetylcholine receptors (nAChR). Although the role of nicotine in cancerogenesis is still discussed controversially, it has been recently shown that nicotine induces DNA damages, via induction of oxidative stress, in bronchial epithelial cells. Moreover, nicotine is able to induce muscle sarcomas in A/J mice.In this mini-review we highlight the role of nAChR and nicotine in all cancer phases (induction, promotion and progression). Relevant new findings quoted in literature and some new experiments of our laboratory were reported and discussed.

Working model summarizing nAChR-mediated signaling pathways involved in survival/apoptotic inhibition, proliferation, migration/invasion, EMT and angiogenesis induced by nicotine, Ach or tobacco derived nitrosamines. These signals may lead to cancer. After nicotine binding to homomeric (α7/α9) or heteromeric (α4β2) nAChR, the receptor gates open allowing Ca+2 influx. Ca+2 triggers downstream signal transduction pathways [adapted from Cardinale et al, 2012; Schuller, 2009).Figure optionsDownload high-quality image (107 K)Download as PowerPoint slide