Oncogenic Raf-1 disrupts epithelial tight junctions via downregulation of occludin.
Oncogenic Raf-1 disrupts epithelial tight junctions via downregulation of occludin.
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DOI：
10.1083/jcb.148.4.791
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发表时间：
2000-02-21
期刊：
影响因子：
--
通讯作者：
Mrsny RJ
中科院分区：
文献类型：
--
作者：
Li D;Mrsny RJ
Occludin 是上皮细胞紧密连接 (TJ) 的整合膜蛋白。最近有人提出它在协调 TJ 形成的结构和功能事件中的潜在作用。使用大鼠唾液腺上皮细胞系 (Pa-4) 作为模型系统，我们证明了 occludin 不仅是功能性 TJ 的关键组成部分，而且还控制与上皮肿瘤发生相关的表型变化。将致癌 Raf-1 转染到 Pa-4 细胞中会导致 TJ 功能完全丧失，并获得缺乏细胞与细胞接触生长控制的分层表型。 occludin和claudin-1的表达下调，ZO-1和E-cadherin的分布模式改变。将人类 occludin 基因引入 Raf-1 激活的 Pa-4 细胞中，导致单层表型的重新获得和功能完整的 TJ 的形成。此外，外源性occludin蛋白的存在导致claudin-1蛋白水平恢复，闭合小带1蛋白（ZO-1）重新定位到TJ，以及E-钙粘蛋白重新分布到侧膜。此外，occludin 的表达抑制了软琼脂糖中 Raf-1 激活的 Pa-4 细胞的贴壁独立生长。因此，occludin 可能在致癌 Raf-1 诱导的 TJ 破坏中充当关键信号分子，并调节与上皮细胞转化相关的表型变化。
Occludin is an integral membrane protein of the epithelial cell tight junction (TJ). Its potential role in coordinating structural and functional events of TJ formation has been suggested recently. Using a rat salivary gland epithelial cell line (Pa-4) as a model system, we have demonstrated that occludin not only is a critical component of functional TJs but also controls the phenotypic changes associated with epithelium oncogenesis. Transfection of an oncogenic Raf-1 into Pa-4 cells resulted in a complete loss of TJ function and the acquisition of a stratified phenotype that lacked cell–cell contact growth control. The expression of occludin and claudin-1 was downregulated, and the distribution patterns of ZO-1 and E-cadherin were altered. Introduction of the human occludin gene into Raf-1–activated Pa-4 cells resulted in reacquisition of a monolayer phenotype and the formation of functionally intact TJs. In addition, the presence of exogenous occludin protein led to a recovery in claudin-1 protein level, relocation of the zonula occludens 1 protein (ZO-1) to the TJ, and redistribution of E-cadherin to the lateral membrane. Furthermore, the expression of occludin inhibited anchorage-independent growth of Raf-1–activated Pa-4 cells in soft agarose. Thus, occludin may act as a pivotal signaling molecule in oncogenic Raf- 1–induced disruption of TJs, and regulates phenotypic changes associated with epithelial cell transformation.
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DOI：
10.1073/pnas.92.17.7686
发表时间：
1995-08-15
影响因子：
11.1
作者：
DUDLEY, DT;PANG, L;SALTIEL, AR
通讯作者：
SALTIEL, AR
影响因子：
1.5
作者：
Kojima, T;Sawada, N;Mochizuki, Y
通讯作者：
Mochizuki, Y
单个基因产物Claudin -1或-2，在成纤维细胞中重构紧密结合的连接链和新兵。
影响因子：
7.8
作者：
Furuse, M;Sasaki, H;Fujimoto, K;Tsukita, S
通讯作者：
Tsukita, S
DOI：
10.1083/jcb.141.7.1539
发表时间：
1998-06-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Furuse M;Fujita K;Hiiragi T;Fujimoto K;Tsukita S
通讯作者：
Tsukita S
影响因子：
7.5
作者：
Marshall, CJ
通讯作者：
Marshall, CJ