α5-nAChR modulates melanoma growth through the Notch1 signaling pathway |
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| Authors: | NingNing Dang Xianguang Meng Guojing Qin Yunhe An QianQian Zhang Xiaoyan Cheng Shuhong Huang |
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| Institution: | 1. Department of Dermatology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, China;2. Beijing Center for Physical and Chemical Analysis, Beijing, China;3. Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, China;4. Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China |
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| Abstract: | The roles of α5-nicotinic acetylcholine receptors (α5-nAChRs) in various types of solid cancer have been reported; however, its role in melanoma remains unknown. We knocked down α5-nAChR expression in melanoma cells to investigate the role of α5-nAChR in the proliferation, migration, and invasion of melanoma cells, and its effect on downstream signaling pathways. Using immunohistochemical analysis, we determined that α5-nAChR expression is significantly increased in human melanoma tissues and cell lines compared with normal human skin tissues. Knocking down α5-nAChR expression in melanoma cells in culture significantly inhibited the proliferation, migration, and invasiveness of melanoma cell lines. Specifically, knockdown of α5-nAChR inhibited PI3K-AKT and ERK1/2 signaling activity. Moreover, we confirmed that the Notch1 signaling pathway is the downstream target of α5-nAChR in melanoma. Our findings suggest that α5-nAChR plays a critical role in melanoma development and progression, and that targeting α5-nAChR may be a strategy for melanoma treatment. |
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| Keywords: | ERK1/2 melanoma Notch1 PI3K α5-nAChR |
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