Claudin-7 inhibits human lung cancer cell migration and invasion through ERK/MAPK signaling pathway.
Claudin-7 inhibits human lung cancer cell migration and invasion through ERK/MAPK signaling pathway.
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DOI：
10.1016/j.yexcr.2011.05.019
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发表时间：
2011-08-01
影响因子：
3.7
通讯作者：
Chen, Yan-Hua
中科院分区：
文献类型：
--
作者：
Lu, Zhe;Ding, Lei;Hong, Heng;Hoggard, John;Lu, Qun;Chen, Yan-Hua
紧密连接是上皮细胞屏障和极性功能关键的连接复合体的最顶端组分。虽然它的破坏是有据可查的癌症进展过程中，如上皮-间充质转化，紧密连接整合膜蛋白claudins影响这一过程的分子机制仍然在很大程度上是未知的。在这份报告中，我们发现claudin-7在人肺的支气管上皮细胞中正常表达，但在肺癌中其分布模式被下调或破坏。为了研究claudin-7在肺癌细胞中的功能，我们将claudin-7 cDNA转染到NCI-H1299中，NCI-H1299是一种没有可检测到的claudin-7表达的人肺癌细胞系。我们发现表达claudin-7的细胞对肝细胞生长因子（HGF）处理的反应降低，运动性降低，形成的足突比对照细胞少。此外，用claudin-7转染的细胞在HGF处理后显著降低了它们的侵袭能力。这些作用是通过MAPK信号通路介导的，因为在claudin-7转染的细胞中ERK 1/2的磷酸化水平显著低于对照细胞。选择性ERK/MAPK通路抑制剂PD 98059能阻断这种运动效应。紧密连接蛋白-7与紧密连接蛋白-1和紧密连接蛋白-3形成稳定的复合物，并且能够将它们募集到紧密连接蛋白-7转染的细胞中的细胞-细胞连接区域。当将对照和claudin-7转染的细胞接种到裸鼠中时，表达claudin-7的细胞产生比对照细胞更小的肿瘤。综上所述，我们的研究表明，claudin-7抑制细胞迁移和侵袭通过ERK/MAPK信号通路在响应于人肺癌细胞生长因子刺激。
Tight junctions are the most apical component of the junctional complex critical for epithelial cell barrier and polarity functions. Although its disruption is well documented during cancer progression such as epithelial-mesenchymal transition, molecular mechanisms by which tight junction integral membrane protein claudins affect this process remain largely unknown. In this report, we found that claudin-7 was normally expressed in bronchial epithelial cells of human lungs but was either downregulated or disrupted in its distribution pattern in lung cancer. To investigate the function of claudin-7 in lung cancer cells, we transfected claudin-7 cDNA into NCI-H1299, a human lung carcinoma cell line that has no detectable claudin-7 expression. We found that claudin-7 expressing cells showed a reduced response to hepatocyte growth factor (HGF) treatment, were less motile, and formed fewer foot processes than the control cells did. In addition, cells transfected with claudin-7 dramatically decreased their invasive ability after HGF treatment. These effects were mediated through the MAPK signaling pathway since the phosphorylation level of ERK1/2 was significantly lower in claudin-7 transfected cells than in control cells. PD98059, a selective inhibitor of ERK/MAPK pathway, was able to block the motile effect. Claudin-7 formed stable complexes with claudin-1 and -3 and was able to recruit them to the cell-cell junction area in claudin-7 transfected cells. When control and claudin-7 transfected cells were inoculated into nude mice, claudin-7 expressing cells produced smaller tumors than the control cells. Taken together, our study demonstrates that claudin-7 inhibits cell migration and invasion through ERK/MAPK signaling pathway in response to growth factor stimulation in human lung cancer cells.
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DOI：
10.1152/ajplung.00182.2003
发表时间：
2003-11-01
影响因子：
4.9
作者：
Coyne, CB;Gambling, TM;Johnson, LG
通讯作者：
Johnson, LG
影响因子：
3.2
作者：
Lawrence, Ryan E.;Salgia, Ravi
通讯作者：
Salgia, Ravi
影响因子：
7.5
作者：
Paschoud, Serge;Bongiovanni, Massimo;Citi, Sandra
通讯作者：
Citi, Sandra
影响因子：
3.8
作者：
Hewitt, Kyle J.;Agarwal, Rachana;Morin, Patrice J.
通讯作者：
Morin, Patrice J.
影响因子：
11.2
作者：
Jedeszko C;Victor BC;Podgorski I;Sloane BF
通讯作者：
Sloane BF