Oncotarget

Research Papers:

Essential role of Na+/Ca2+ exchanger 1 in smoking-induced growth and migration of esophageal squamous cell carcinoma

Jiexia Wen, Yan Pang, Tao Zhou, Ximing Qi, Min Zhao, Bin Xuan, Xiangcai Meng, Yunsheng Guo, Qingbin Liu, Huagang Liang, Yang Li, Hui Dong and Yimin Wang _

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Oncotarget. 2016; 7:63816-63828. https://doi.org/10.18632/oncotarget.11695

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Abstract

Jiexia Wen1,*, Yan Pang1,*, Tao Zhou2, Ximing Qi1, Min Zhao4, Bin Xuan2, Xiangcai Meng2, Yunsheng Guo2, Qingbin Liu2, Huagang Liang5, Yang Li1, Hui Dong1,3, Yimin Wang1,2

1Department of Central Laboratory, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China

2Department of General Surgery, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China

3Department of Medicine, University of California, San Diego, California, USA

4Department of Pathology, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China

5Department of Thoracic Surgery, First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China

*These authors equally contributed to this work

Correspondence to:

Yimin Wang, email: [email protected]

Hui Dong, email: [email protected]

Keywords: Na+/Ca2+ exchanger 1, calcium signaling, cigarette smoking, esophageal squamous cell carcinoma, tumorigenesis

Received: April 23, 2016     Accepted: August 24, 2016     Published: August 30, 2016

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.


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