Expression of aquaporin 5 increases proliferation and metastasis potential of lung cancer
Expression of aquaporin 5 increases proliferation and metastasis potential of lung cancer
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水通道蛋白5的表达增加肺癌的增殖和转移潜力
DOI：
10.1002/path.2702
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发表时间：
2010-06-01
影响因子：
7.3
通讯作者：
Bai, Chunxue
中科院分区：
文献类型：
--
作者：
Zhang, Ziqiang;Chen, Zhihong;Bai, Chunxue
水通道水通道蛋白5 （AQP5）在肺泡I型上皮细胞的顶膜高度表达，具有较高的水渗透性。AQP5在肺癌组织中也有表达。既往研究表明，AQP5在癌组织中表达水平较周围正常组织上调。此外，AQP5在肺癌组织中的表达与预后不良相关。在此，我们测试了AQP5在肺癌发生发展中的作用。利用不同AQP5表达的肺癌细胞，研究细胞增殖和迁移这两个重要的肿瘤细胞生物学参数。我们发现AQP5高表达的癌细胞的增殖和迁移潜力增强，而AQP5低表达的癌细胞的增殖和转移潜力降低。癌基因分析显示，转染AQP5的细胞中PCNA和c-myc表达显著升高。AQP5转染后的细胞MUC5AC粘蛋白表达也显著升高，这可能与肺癌转移潜力增强有关。AQP5过表达导致癌细胞中表皮生长因子受体（EGFR）、细胞外受体激酶（ERK1/2）和p38丝裂原活化蛋白激酶（p38 MAPK）通路的激活增强。此外，AQP5基因敲除小鼠肺中EGFR/ERK/p38 MAPK通路的激活降低，而AQP1或AQP3基因敲除小鼠肺组织中EGFR/ERK/p38 MAPK通路的激活未发生显著变化。综上所述，我们的研究结果为AQP5促进肺癌细胞增殖和迁移提供了证据，可能通过激活EGFR/ERK/p38 MAPK信号通路，但为什么AQP5而不是其他水通道蛋白表达影响EGFR/ERK/p38 MAPK通路仍有待进一步探索。版权所有(C) 2010英国和爱尔兰病理学会。约翰·威利父子有限公司出版。
Water channel aquaporin 5 (AQP5) is highly expressed at the apical membrane of alveolar type I epithelial cells and confers high osmotic water permeability. AQP5 is also expressed in lung cancer tissue. Previous studies showed there was an up-regulation of AQP5 expression in cancer tissue compared to surrounding normal tissue. In addition, expression of AQP5 in lung cancer tissue was associated with poor prognosis. Herein, we tested the role of AQP5 in lung cancer oncogenesis and development. Lung cancer cells with different expression of AQP5 were used to study cell proliferation and migration, two important parameters for tumour cell biology. We found enhanced proliferation and migration potential in cancer cells with high AQP5 expression, while reduced proliferation and metastasis potential in cancer cells with low AQP5 expression. Oncogene analysis showed significantly increased PCNA and c-myc expression in AQP5 transfected cells. AQP5 transfected cells also showed significant increased MUC5AC mucin expression, which might contribute to the enhanced metastasis potential of lung cancer. AQP5 overexpression resulted in enhanced activation of the epidermal growth factor receptor (EGFR), extracellular receptor kinase (ERK1/2), and p38 mitogen-activated protein kinase (p38 MAPK) pathway in cancer cells. Moreover, deletion of AQP5 demonstrated decreased activation of the EGFR/ERK/p38 MAPK pathway in AQP5 knockout mice lungs, while deletion of AQP1 or AQP3 did not exhibit significant changes on activation of the EGFR/ERK/p38 MAPK pathway in lung tissue. In conclusion, our results provide evidence for AQP5-facilitated lung cancer cell proliferation and migration, possibly through activation of the EGFR/ERK/p38 MAPK signalling pathway, but why AQP5 but not other aquaporin expression affects the EGFR/ERK/p38 MAPK pathway still needs further exploration. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.