α5-nAChR modulates melanoma growth through the Notch1 signaling pathway

被引:14
作者
Dang, NingNing [1 ]
Meng, Xianguang [1 ]
Qin, Guojing [1 ]
An, Yunhe [2 ]
Zhang, QianQian [3 ]
Cheng, Xiaoyan [2 ]
Huang, Shuhong [4 ]
机构
[1] Shandong Univ, Jinan Cent Hosp, Dept Dermatol, 105 Jiefang Rd, Jinan 250013, Shandong, Peoples R China
[2] Beijing Ctr Phys & Chem Anal, Beijing, Peoples R China
[3] Shandong First Med Univ & Shandong Acad Med Sci, Tai An, Shandong, Peoples R China
[4] Shandong First Med Univ & Shandong Acad Med Sci, Inst Basic Med, 18877 Jingshi Rd, Jinan, Shandong, Peoples R China
基金
中国国家自然科学基金; 中国博士后科学基金;
关键词
ERK1; 2; melanoma; Notch1; PI3K; alpha; 5-nAChR; LUNG-CANCER; NICOTINE; SMOKING; RISK;
D O I
10.1002/jcp.29435
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:7816 / 7826
页数:11
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