Molecular mechanisms leading to loss of differentiation and gain of invasiveness in epithelial cells
Molecular mechanisms leading to loss of differentiation and gain of invasiveness in epithelial cells
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DOI：
10.1242/jcs.1993.supplement_17.23
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发表时间：
1993-12
影响因子：
4
通讯作者：
W. Birchmeier;Weidner Km;J. Behrens
中科院分区：
文献类型：
--
作者：
W. Birchmeier;Weidner Km;J. Behrens
一段时间以来，人们已经认识到，癌中上皮分化的丧失，伴随着肿瘤细胞的更高的移动性和侵袭性，是细胞间粘附减少的结果。最近的各种报道表明，在浸润性癌中细胞“分散”的主要原因是细胞间连接的完整性丧失。因此，上皮粘附连接的几种组分（如E-钙粘蛋白、α-连环蛋白）的表达或结构可能出现缺陷，我们对连接分子的了解增加，使得在某些情况下可以用分子术语解释这些缺陷。此外，连接组分（例如β-连环蛋白）的酪氨酸磷酸化似乎在细胞-细胞接触的组装和分解中起作用。上皮连接形成的一些效应物是酪氨酸蛋白激酶，例如分散因子/肝细胞生长因子受体c-Met、FGF受体和pp 60 src激酶。酪氨酸磷酸化在肿瘤发展过程中的重要性越来越明显。
SUMMARY It has been realized for some time that the loss of epithelial differentiation in carcinomas, which is accompanied by higher mobility and invasiveness of the tumor cells, is a consequence of reduced intercellular adhesion. A variety of recent reports have indicated that the primary cause for the ‘scattering’ of the cells in invasive carcinomas is a loss of the integrity of intercellular junctions. Thus, defects in expression or structure of several components of the epithelial adherens junctions (e.g. E-cadherin, α-catenin) can occur, and our increased knowledge about the molecules of the junctions allows an explanation of these defects in molecular terms in some of the cases. Furthermore, tyrosine phosphorylation of junctional components (e.g. β-catenin) appears to play a role in the assembly and disassembly of cell-cell contacts. Some of the effectors of epithelial junction formation are tyrosine protein kinases, e.g. the scatter factor/hepatocyte growth factor receptor c-Met, the FGF receptors and the pp60src kinase. The importance of tyrosine phosphorylation in junctions during tumor development is becoming increasingly evident.