The alpha9 nicotinic acetylcholine receptor is the key mediator in nicotine-enhanced cancer metastasis in breast cancer cells

Background/purpose: The tobacco-specific mitogen nicotine was reported to correlate with cancer progression and tumorigenesis in breast cancer. Metastasis is a major cause of cancer death, so the influence of nicotine on breast cancer cell migration is also of interest. Our aim is to elucidate the mechanisms of nicotine-enhanced migration of breast cancer cells and thereby achieve better control of metastasis. Methods: The influence of nicotine on breast cancer cell migration was evaluated by trans-well and wound-healing migration assays. Receptor-mediated migration was studied with both a small molecule inhibitor and small interfering RNA (siRNA). Results: The alpha9 nicotinic acetylcholine receptor, α9nAChR, was identified in breast cancer cell lines MCF-7 and MDA-MB-231. Nicotine enhanced cell migration in both trans-well and wound-healing migration assays. We used a specific inhibitor and siRNA to demonstrate that α9nAChR is the key modulator in mediating nicotine-enhanced breast cancer cell migration through up-regulation of fibronectin and vimentin. Conclusion: Nicotine treatment enhanced breast cancer metastasis through α9nAChR signaling via enhanced fibronectin and vimentin expression.