Aquaporin 3 promotes the stem-like properties of gastric cancer cells via Wnt/GSK-3β/β-catenin pathway
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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
Lizong Shen, e-mail: firstname.lastname@example.org.
Keywords: gastric cancer, aquaporin 3, cancer stem cells (CSCs), CD44
Received: January 12, 2016 Accepted: February 11, 2016 Published: February 24, 2016
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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