Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
Cold Spring Harb Perspect Biol. 2010 Feb;2(2):a002915. doi: 10.1101/cshperspect.a002915.
The epithelial-mesenchymal transition is essential in both embryonic development and the progression of carcinomas. Wnt signaling and cadherin-mediated adhesion have been implicated in both processes; clarifying their role will depend on linking them to rearrangements of cellular structure and behavior. beta-Catenin is an essential molecule both in cadherin-mediated cell adhesion and in canonical Wnt signaling. Numerous experiments have shown that the loss of cadherin-mediated cell adhesion can promote beta-catenin release and signaling; this is accomplished by proteases, protein kinases and other molecules. Cadherin loss can also signal to several other regulatory pathways. Additionally, many target genes of Wnt signaling influence cadherin adhesion. The most conspicuous of these Wnt target genes encode the transcription factors Twist and Slug, which directly inhibit the E-cadherin gene promoter. Other Wnt/beta-catenin target genes encode metalloproteases or the cell adhesion molecule L1, which favor the degradation of E-cadherin. These factors provide a mechanism whereby cadherin loss and increased Wnt signaling induce epithelial-mesenchymal transition in both carcinomas and development.
上皮-间充质转化在胚胎发育和癌的进展中都是必不可少的。Wnt 信号和钙黏蛋白介导的黏附都与这两个过程有关；阐明它们的作用将取决于将它们与细胞结构和行为的重排联系起来。β-连环蛋白在钙黏蛋白介导的细胞黏附和经典 Wnt 信号中都是必需的分子。大量实验表明，钙黏蛋白介导的细胞黏附的丧失可以促进β-连环蛋白的释放和信号转导；这是通过蛋白酶、蛋白激酶和其他分子来实现的。钙黏蛋白的丧失也可以向其他几个调节途径发出信号。此外，Wnt 信号的许多靶基因影响钙黏蛋白的黏附。其中最明显的 Wnt 靶基因编码转录因子 Twist 和 Slug，它们直接抑制 E-钙黏蛋白基因启动子。其他 Wnt/β-连环蛋白靶基因编码金属蛋白酶或细胞黏附分子 L1，它们有利于 E-钙黏蛋白的降解。这些因素提供了一种机制，通过这种机制，钙黏蛋白的丧失和 Wnt 信号的增加在癌和发育中诱导上皮-间充质转化。
