Expression of inappropriate cadherins by epithelial tumor cells promotes endocytosis and degradation of E-cadherin via competition for p120ctn
Expression of inappropriate cadherins by epithelial tumor cells promotes endocytosis and degradation of E-cadherin via competition for p120ctn
复制标题
DOI：
10.1038/sj.onc.1209396
复制
发表时间：
2006-08-03
期刊：
影响因子：
8
通讯作者：
Johnson, K. R.
中科院分区：
文献类型：
--
作者：
Maeda, M.;Johnson, E.;Johnson, K. R.
钙粘蛋白细胞间粘附蛋白在调节肿瘤细胞的行为中起重要作用。E-钙粘蛋白作为肿瘤细胞侵袭的抑制因子，并且当肿瘤细胞开启非上皮钙粘蛋白的表达时，它们通常表达较少的E-钙粘蛋白，增强细胞的致瘤表型。在这里，我们表明，当A431细胞被迫表达R-钙粘蛋白，他们显着下调内源性E-和P-钙粘蛋白的表达。此外，我们表明，这种下调是由于增加营业额的内源性钙粘蛋白通过网格蛋白依赖性内吞作用。p120（ctn）与经典钙粘蛋白的近膜结构域结合，并被认为可以调节钙粘蛋白的粘附活性。p120（ctn）可能实现这一点的一种方式是作为变阻器来调节钙粘蛋白的水平。在这里，我们表明，降解的E-钙粘蛋白的R-钙粘蛋白的表达是由于竞争p120（ctn）。
Cadherin cell-cell adhesion proteins play an important role in modulating the behavior of tumor cells. E-cadherin serves as a suppressor of tumor cell invasion, and when tumor cells turn on the expression of a non-epithelial cadherin, they often express less E-cadherin, enhancing the tumorigenic phenotype of the cells. Here, we show that when A431 cells are forced to express R-cadherin, they dramatically downregulate the expression of endogenous E- and P-cadherin. In addition, we show that this downregulation is owing to increased turnover of the endogenous cadherins via clathrin-dependent endocytosis. p120(ctn) binds to the juxtamembrane domain of classical cadherins and has been proposed to regulate cadherin adhesive activity. One way p120(ctn) may accomplish this is to serve as a rheostat to regulate the levels of cadherin. Here, we show that the degradation of E-cadherin in response to expression of R-cadherin is owing to competition for p120(ctn).