Oncotarget

Research Papers:

Aquaporin 3 promotes the stem-like properties of gastric cancer cells via Wnt/GSK-3β/β-catenin pathway

Yangchun Zhou, Yao Wang, Jianfei Wen, Haijian Zhao, Xuqiang Dong, Zhihong Zhang, Shoulin Wang and Lizong Shen _

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Oncotarget. 2016; 7:16529-16541. https://doi.org/10.18632/oncotarget.7664

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Abstract

Yangchun Zhou1,2,*, Yao Wang1,*, Jianfei Wen1,*, Haijian Zhao1,3, Xuqiang Dong1, Zhihong Zhang4, Shoulin Wang5, Lizong Shen1

1Division of Gastrointestinal Surgery, Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China

2Department of General Surgery, Sir Run Run Shaw Hospital, Third Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China

3Division of Gastrointestinal Surgery, Department of General Surgery, Affiliated Huai’an Hospital, Xuzhou Medical College, Huai’an, Jiangsu, China

4Department of Pathology, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China

5School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China

*These authors contributed equally to this work

Correspondence to:

Lizong Shen, e-mail: shenlz@njmu.edu.cn.

Keywords: gastric cancer, aquaporin 3, cancer stem cells (CSCs), CD44

Received: January 12, 2016     Accepted: February 11, 2016     Published: February 24, 2016

ABSTRACT

Cancer stem cells (CSCs) are believed to contribute to the tumor growth in gastric carcinoma (GC), a common lethal malignancy. This study investigated the effect of aquaporin 3 (AQP3) on stem-like properties of human GC cells. Elevated AQP3 expression was associated with CD44 expression in human GC specimens. Expression of AQP3 and that of CD44 positively correlated with Lauren classification, lymph node metastasis, and lymphovascular invasion. Altering the AQP3 expression had pronounced effects on the tumorigenic potential and self-renewal capacity of the gastric cancer cell lines SGC7901, MGC803, and AGS, both in vitro and in vivo. Overexpression of AQP3 induced CD44 expression and activation of the β-catenin signaling pathway, whereas silencing AQP3 expression using short hairpin RNA had the opposite effect. Furthermore, pharmacological inhibition of GSK-3β using LiCl impaired the effect of AQP3 knockdown in CSCs, whereas the inhibition of the Wnt/β-catenin pathway by XAV939 blocked the effect of AQP3 overexpression. These results demonstrate that AQP3 promotes stem-like properties of human GC cells by activating the Wnt/GSK-3β/β-catenin signaling pathway.


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