Aquaporin 3 promotes the stem-like properties of gastric cancer cells via Wnt/GSK-3β/β-catenin pathway.
Aquaporin 3 promotes the stem-like properties of gastric cancer cells via Wnt/GSK-3β/β-catenin pathway.
复制标题
水通道蛋白 3 通过 Wnt/GSK-3β/β-连环蛋白途径促进胃癌细胞的干细胞特性
DOI：
10.18632/oncotarget.7664
复制
发表时间：
2016-03-29
期刊：
影响因子：
--
通讯作者：
Shen L
中科院分区：
文献类型：
--
作者：
Zhou Y;Wang Y;Wen J;Zhao H;Dong X;Zhang Z;Wang S;Shen L
胃癌是一种常见的恶性肿瘤，肿瘤干细胞（cancer stem cells，CSCs）被认为与胃癌的生长有关。本研究探讨了水通道蛋白3（AQP3）对人胃癌细胞干细胞样特性的影响。在人胃癌标本中，AQP3表达升高与CD44表达相关。AQP3和CD44的表达与Lauren分级、淋巴结转移和淋巴管浸润呈正相关。改变AQP3的表达对胃癌细胞系SGC7901、MGC803和AGS的成瘤潜力和自我更新能力具有显著的影响，无论是在体外还是在体内。AQP3的过表达诱导了CD44的表达和β-catenin信号通路的激活，而使用短发夹RNA沉默AQP3的表达具有相反的效果。此外，使用LiCl的GSK-3 β的药理学抑制削弱了CSCs中AQP3敲低的作用，而XAV 939对Wnt/β-连环蛋白通路的抑制阻断了AQP3过表达的作用。这些结果表明，AQP3通过激活Wnt/GSK-3 β/β-catenin信号通路促进人GC细胞的干细胞样特性。
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.