Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a dispersed carcinoma line.
Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a dispersed carcinoma line.
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DOI：
10.1083/jcb.127.1.247
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发表时间：
1994-10
期刊：
影响因子：
--
通讯作者：
Takeichi M
中科院分区：
文献类型：
--
作者：
Watabe M;Nagafuchi A;Tsukita S;Takeichi M
尽管PC9肺癌细胞表达E-钙粘蛋白，但由于缺乏钙粘附素相关蛋白--α-连环蛋白，PC9肺癌细胞不能彼此紧密结合，因此只能单独生长。然而，当E-钙粘蛋白被α-连环蛋白基因所激活时，它们形成球形聚集体，每个聚集体由一个封闭的单层细胞片组成。在目前的工作中，我们通过检测不同的细胞黏附分子在细胞层表面的分布，包括E-钙粘蛋白、ZO-1、桥粒粘连蛋白、整合素和层粘连蛋白，来检测α-连环蛋白转基因细胞层是否表达上皮表型。在未转染的PC9细胞中，所有这些分子都随机分布在细胞表面。然而，在转基因细胞中，它们中的每一个都被重新分布到一个特征的极化模式中，而表达量没有变化。电子显微镜观察发现，转导α-连环素的细胞层获得了典型的单层上皮细胞的顶基两极；它们仅在聚集体的外表面形成微绒毛，由紧密连接、粘连连接和桥粒组成的连接复合体按顺序排列。这些结果表明，E-钙粘附素的激活触发了连接复合体的形成和细胞表面蛋白质和结构的极化分布。我们还发现，在未转染的PC9细胞中，ZO-1与E-钙粘蛋白形成密集簇并共定位，而其他黏附分子很少与E-钙粘蛋白共定位，这表明即使在没有细胞-细胞接触的情况下，ZO-1与E-钙粘蛋白之间也存在某种特异性的相互作用。此外，我们还发现E-钙粘附素的激活导致PC9细胞生长受阻。因此，我们得出结论，E-钙粘附素-连环素黏附系统不仅对上皮细胞的结构组织至关重要，而且对其生长控制也是必不可少的。
PC9 lung carcinoma cells cannot tightly associate with one another, and therefore grow singly, despite their expression of E-cadherin, because of their lack of alpha-catenin, a cadherin-associated protein. However, when the E-cadherin is activated by transfection with alpha-catenin cDNA, they form spherical aggregates, each consisting of an enclosed monolayer cell sheet. In the present work, we examined whether the alpha-catenin-transfected cell layers expressed epithelial phenotypes, by determining the distribution of various cell adhesion molecules on their surfaces, including E-cadherin, ZO-1, desmoplakin, integrins, and laminin. In untransfected PC9 cells, all these molecules were randomly distributed on their cell surface. In the transfected cells, however, each of them was redistributed into a characteristic polarized pattern without a change in the amount of expression. Electron microscopic study demonstrated that the alpha-catenin-transfected cell layers acquired apical-basal polarity typical of simple epithelia; they formed microvilli only on the outer surface of the aggregates, and a junctional complex composed of tight junction adherens junction, and desmosome arranged in this order. These results indicate that the activation of E-cadherin triggered the formation of the junctional complex and the polarized distribution of cell surface proteins and structures. We also found that, in untransfected PC9 cells, ZO-1 formed condensed clusters and colocalized with E-cadherin, but that other adhesion molecules rarely showed such colocalization with E-cadherin, suggesting that there is some specific interaction between ZO-1 and E- cadherin even in the absence of cell-cell contacts. In addition, we found that the activation of E-cadherin caused a retardation of PC9 cell growth. Thus, we concluded that the E-cadherin-catenin adhesion system is essential not only for structural organization of epithelial cells but also for the control of their growth.