N-Cadherin extracellular repeat 4 mediates epithelial to mesenchymal transition and increased motility.
N-Cadherin extracellular repeat 4 mediates epithelial to mesenchymal transition and increased motility.
复制标题
DOI：
10.1083/jcb.151.6.1193
复制
发表时间：
2000-12-11
期刊：
影响因子：
--
通讯作者：
Johnson KR
中科院分区：
文献类型：
--
作者：
Kim JB;Islam S;Kim YJ;Prudoff RS;Sass KM;Wheelock MJ;Johnson KR
E-钙粘蛋白和N-钙粘蛋白是经典的钙粘蛋白家族的成员。E-钙粘附素在维持上皮细胞正常表型方面起着重要作用。我们实验室和其他实验室以前的研究表明，来自上皮组织的肿瘤细胞不适当地表达N-钙粘素会导致细胞转化为更多的成纤维细胞样细胞，从而增加运动性和侵袭性。我们目前的研究旨在确定N-钙粘蛋白的哪些结构域使其在改变细胞行为方面与E-钙粘蛋白不同，例如哪些结构域负责上皮向间充质的转变以及细胞运动和侵袭的增加。为了解决这个问题，我们构建了由选定的E-和N-钙粘附素结构域组成的嵌合型钙粘附素。将嵌合体导入上皮细胞，以确定它们对细胞形态和细胞行为的影响。我们发现，N-钙粘附素EC-4的69个氨基酸部分对于促进鳞状上皮细胞上皮向间充质转化和增加细胞运动性是必要的，也是足够的。在这里，我们展示了不同的钙粘素家族成员促进不同的细胞行为。此外，我们还发现了一种新的活性，可归因于N-钙粘蛋白的胞外结构域。
E- and N-cadherin are members of the classical cadherin family of proteins. E-cadherin plays an important role in maintaining the normal phenotype of epithelial cells. Previous studies from our laboratory and other laboratories have shown that inappropriate expression of N-cadherin by tumor cells derived from epithelial tissue results in conversion of the cell to a more fibroblast-like cell, with increased motility and invasion. Our present study was designed to determine which domains of N-cadherin make it different from E-cadherin, with respect to altering cellular behavior, such as which domains are responsible for the epithelial to mesenchymal transition and increased cell motility and invasion. To address this question, we constructed chimeric cadherins comprised of selected domains of E- and N-cadherin. The chimeras were transfected into epithelial cells to determine their effect on cell morphology and cellular behavior. We found that a 69–amino acid portion of EC-4 of N-cadherin was necessary and sufficient to promote both an epithelial to mesenchymal transition in squamous epithelial cells and increased cell motility. Here, we show that different cadherin family members promote different cellular behaviors. In addition, we identify a novel activity that can be ascribed to the extracellular domain of N-cadherin.