We previously demonstrated that nicotine stimulates non small cell lung carcinoma (NSCLC) cell proliferation through nicotinic acetylcholine receptor (nAChR)-mediated induction of fibronectin expression. However, the mechanisms by which this agent affects human lung cancer occurrence and progression remain incompletely elucidated. Here, we show that nicotine increases the expression of integrin-linked kinase (ILK), a unique intracellular adaptor and kinase that has been implicated in the regulation of cancer cell growth/survival. This effect was blocked by the α7 nAChR antagonist, α-bungarotoxin, and by α7 nAChR siRNA. Silencing of ILK blocked the stimulatory effect of nicotine on phosphorylation of the PI3-K downstream target Akt and on cell growth. Furthermore, nicotine increased ILK gene promoter activity through inhibition of transcription factor AP-2α protein expression. Silencing of AP-2α enhanced, while exogenous expression of AP-2α attenuated, the stimulatory effect of nicotine on ILK expression. These findings appear to be relevant in vivo since we found that nicotine treatment increased tumor growth in animal models. Collectively, our results demonstrate that nicotine increases ILK gene expression through α7 nAChR-mediated inhibition of AP-2α followed by stimulation of PI3-K/Akt signaling. In turn, this leads to increased NSCLC cell growth. This study unveils a novel mechanism by which nicotine promotes human lung carcinoma cell growth/survival.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1230.