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

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.

• Authors: Yangchun Zhou, Yao Wang, Jianfei Wen, Haijian Zhao, Xuqiang Dong, Zhihong Zhang, Shoulin Wang, Lizong Shen
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 13 Pg. 16529-41 (Mar 29 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 26918728 (Publication Type: Journal Article)

Chemical References

• Heterocyclic Compounds, 3-Ring
• XAV939
• beta Catenin
• Aquaporin 3
• Glycogen Synthase Kinase 3
• Lithium Chloride

Topics

• Adult
• Aged
• Animals
• Aquaporin 3 (genetics, metabolism)
• Blotting, Western
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic
• Glycogen Synthase Kinase 3 (antagonists & inhibitors, metabolism)
• Heterocyclic Compounds, 3-Ring (pharmacology)
• Humans
• Lithium Chloride (pharmacology)
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Neoplastic Stem Cells (metabolism)
• RNA Interference
• Reverse Transcriptase Polymerase Chain Reaction
• Stomach Neoplasms (genetics, metabolism, pathology)
• Transplantation, Heterologous
• Wnt Signaling Pathway (drug effects)
• beta Catenin (antagonists & inhibitors, metabolism)