Aquaporin 3 promotes epithelial-mesenchymal transition in gastric cancer.

Aquaporin 3 promotes epithelial-mesenchymal transition in gastric cancer.
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水通道蛋白3促进胃癌上皮间质转化

DOI:
10.1186/1756-9966-33-38
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发表时间:
2014-05-03
期刊:
Journal of experimental & clinical cancer research : CR
影响因子:
--
通讯作者:
Shen LZ
Shen LZ
中科院分区:
其他
文献类型:
--
作者:
Chen J;Wang T;Zhou YC;Gao F;Zhang ZH;Xu H;Wang SL;Shen LZ

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背景胃癌(GC)是一种常见的致命性恶性肿瘤,上皮-间充质转化(EMT)被认为与肿瘤的侵袭和转移有关。水通道蛋白3(AQP3)在人胃癌组织中高表达,而人表皮生长因子(EGF)和肝细胞生长因子可诱导内皮细胞转化,上调AQP3的表达,从而促进胃癌细胞的迁移和增殖。方法采用免疫组织化学方法检测AQP3和EMT相关蛋白在人胃癌组织中的表达,并评价其临床意义。用小干扰RNA抑制AQP3的表达,而用EGF上调AQP3的表达。采用Western blotting、实时定量聚合酶链式反应和免疫荧光技术检测AQP3和EMT相关蛋白在人胃癌细胞系SGC7901和MGC803中的表达变化。结果人胃癌组织中AQP3表达上调与EMT相关蛋白的表达呈正相关,与胃癌预后不良相关。AQP3在体外调控GC细胞的增殖、迁移和侵袭,并诱导E-钙粘附素的抑制。AQP3在体外也可上调波形蛋白和纤维连接蛋白的表达。PI3K/AKT/Snail信号通路可能参与了AQP3在GC中诱导EMT的过程。结论AQP3促进人胃癌EMT的发生,有助于我们了解AQP3在GC发生发展中的作用机制,从而为其治疗提供潜在的策略。
BackgroundGastric carcinoma (GC) is a common and lethal malignancy, and epithelial-mesenchymal transition (EMT) is believed to contribute to invasive and metastatic tumor growth. Aquaporin 3 (AQP3) is overexpressed in human GC tissues, while human epidermal growth factor (EGF) and hepatocyte growth factor, which can induce EMT, are able to up-regulate AQP3 expression, subsequently promoting GC cell migration and proliferation. The purpose of this study was to investigate the effects of AQP3 on EMT in human GC.MethodsAQP3 and EMT-related proteins were detected by immunohistochemistry in human GC specimens and their clinical significance evaluated. AQP3 knockdown was attempted using small interfering RNAs, while EGF was used to up-regulate AQP3 expression. Western blotting, real-time quantitative polymerase chain reaction assays and immunofluorescence were used to evaluate changes in expression of AQP3 and EMT-related proteins in the SGC7901 and MGC803 human GC cell lines.ResultsAQP3 up-expression was associated with EMT-related proteins in human GC specimens, which correlated with poor prognosis for GC. AQP3 modulated GC cell proliferation, migration and invasion in vitro, and induced E-cadherin repression. AQP3 also up-regulated the expression of vimentin and fibronectin in vitro. The PI3K/AKT/SNAIL signaling pathway was likely involved in the induction of EMT by AQP3 in GC.ConclusionsAQP3 promotes EMT in human cases of GC, allowing us to understand the mechanisms of AQP3 in GC progression, thus providing a potential strategy for its treatment.
DOI: 10.1007/s10585-011-9404-x
发表时间: 2011-12
影响因子: 4
作者:
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