α5-nAChR modulates melanoma growth through the Notch1 signaling pathway

The roles of alpha 5-nicotinic acetylcholine receptors (alpha 5-nAChRs) in various types of solid cancer have been reported; however, its role in melanoma remains unknown. We knocked down alpha 5-nAChR expression in melanoma cells to investigate the role of alpha 5-nAChR in the proliferation, migration, and invasion of melanoma cells, and its effect on downstream signaling pathways. Using immunohistochemical analysis, we determined that alpha 5-nAChR expression is significantly increased in human melanoma tissues and cell lines compared with normal human skin tissues. Knocking down alpha 5-nAChR expression in melanoma cells in culture significantly inhibited the proliferation, migration, and invasiveness of melanoma cell lines. Specifically, knockdown of alpha 5-nAChR inhibited PI3K-AKT and ERK1/2 signaling activity. Moreover, we confirmed that the Notch1 signaling pathway is the downstream target of alpha 5-nAChR in melanoma. Our findings suggest that alpha 5-nAChR plays a critical role in melanoma development and progression, and that targeting alpha 5-nAChR may be a strategy for melanoma treatment.