title: Essential role of Na+/Ca2+ exchanger 1 in smoking-induced growth and migration of esophageal squamous cell carcinoma.
abstract: Tobacco-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a major environmental risk factor for the pathogenesis of human esophageal squamous cell carcinoma (ESCC). However, the molecular mechanisms by which tobacco induces ESCC are not well understood. Na+/Ca2+ exchanger 1 (NCX1) is a plasma membrane transporter protein that plays an essential role in maintaining cytosolic Ca2+ ([Ca2+]cyt) homeostasis under physiological conditions and is implicated in tumorigenesis as well. In this study, we found that NCX1 expression was significantly higher in ESCC primary tissues compared to the noncancerous tissues and was overexpressed in tumor samples from the smoking patients. The expression of NCX1 proteins was also significantly higher in human ESCC cell lines compared to normal esophageal epithelial cell line. Moreover, NNK potentiated the [Ca2+]cyt signaling induced by removal of extracellular Na+, which was abolished by KB-R7943 or SN-6. NNK dose-dependently promoted proliferation and migration of human ESCC cells induced by NCX1 activation. Therefore, NCX1 expression correlates with the smoking status of ESCC patients, and NNK activates the Ca2+ entry mode of NCX1 in ESCC cells, leading to cell proliferation and migration. Our findings suggest NCX1 protein is a novel potential target for ESCC therapy.
authors: Department of Central Laboratory, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China.
authors: Jiexia
authors: J
authors: Wen
authors: Department of Central Laboratory, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China.
authors: Yan
authors: Y
authors: Pang
authors: Department of General Surgery, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China.
authors: Tao
authors: T
authors: Zhou
authors: Department of Central Laboratory, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China.
authors: Ximing
authors: X
authors: Qi
authors: Department of Pathology, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China.
authors: Min
authors: M
authors: Zhao
authors: Department of General Surgery, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China.
authors: Bin
authors: B
authors: Xuan
authors: Department of General Surgery, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China.
authors: Xiangcai
authors: X
authors: Meng
authors: Department of General Surgery, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China.
authors: Yunsheng
authors: Y
authors: Guo
authors: Department of General Surgery, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China.
authors: Qingbin
authors: Q
authors: Liu
authors: Department of Thoracic Surgery, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China.
authors: Huagang
authors: H
authors: Liang
authors: Department of Central Laboratory, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China.
authors: Yang
authors: Y
authors: Li
authors: Department of Central Laboratory, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China.|Department of Medicine, University of California, San Diego, California, USA.
authors: Hui
authors: H
authors: Dong
authors: Department of Central Laboratory, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China.|Department of General Surgery, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China.
authors: Yimin
authors: Y
authors: Wang
mesh_terms: D001593:Benzyl Compounds / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism*; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D009602:Nitrosamines / Q000009:adverse effects*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D053778:Thiazolidines / Q000737:chemistry; D013890:Thiourea / Q000031:analogs & derivatives / Q000737:chemistry; D062789:Tobacco Products
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; C487681:2-(4-(4-nitrobenzyloxy)benzyl)thiazolidine-4-carboxylic acid ethyl ester; D001593:Benzyl Compounds; D009602:Nitrosamines; D019831:Sodium-Calcium Exchanger; D053778:Thiazolidines; C110374:sodium-calcium exchanger 1; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D012964:Sodium; D013890:Thiourea; D002118:Calcium
keywords: Na+/Ca2+ exchanger 1; calcium signaling; cigarette smoking; esophageal squamous cell carcinoma; tumorigenesis