Shindo Masayo, Wada Housei, Kaido Masako, Tateno Minoru, Aigaki Toshiro, Tsuda Leo, Hayashi Shigeo
Riken Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku Kobe 650-0047, Japan.
Development. 2008 Apr;135(7):1355-64. doi: 10.1242/dev.015982. Epub 2008 Feb 27.
The downregulation of E-cadherin by Src promotes epithelial to mesenchymal transition and tumorigenesis. However, a simple loss of cell adhesion is not sufficient to explain the diverse developmental roles of Src and metastatic behavior of viral Src-transformed cells. Here, we studied the functions of endogenous and activated forms of Drosophila Src in the context of tracheal epithelial development, during which extensive remodeling of adherens junctions takes place. We show that Src42A is selectively activated in the adherens junctions of epithelia undergoing morphogenesis. Src42A and Src64B are required for tracheal development and to increase the rate of adherens junction turnover. The activation of Src42A caused opposing effects: it reduced the E-cadherin protein level but stimulated transcription of the E-cadherin gene through the activation of Armadillo and TCF. This TCF-dependent pathway was essential for the maintenance of E-cadherin expression and for tissue integrity under conditions of high Src activity. Our data suggest that the two opposing outcomes of Src activation on E-cadherin facilitate the efficient exchange of adherens junctions, demonstrating the key role of Src in the maintenance of epithelial integrity.
Src对E-钙黏蛋白的下调促进上皮-间质转化和肿瘤发生。然而，单纯的细胞黏附丧失不足以解释Src的多种发育作用以及病毒Src转化细胞的转移行为。在此，我们在气管上皮发育的背景下研究了果蝇Src内源性和激活形式的功能，在此过程中黏附连接会发生广泛重塑。我们发现Src42A在正在进行形态发生的上皮细胞的黏附连接中被选择性激活。Src42A和Src64B是气管发育所必需的，并且能提高黏附连接更新的速率。Src42A的激活产生了相反的效应：它降低了E-钙黏蛋白的蛋白水平，但通过激活犰狳蛋白和TCF刺激了E-钙黏蛋白基因的转录。这种依赖TCF的途径对于在高Src活性条件下维持E-钙黏蛋白表达和组织完整性至关重要。我们的数据表明，Src激活对E-钙黏蛋白产生的两种相反结果促进了黏附连接的有效交换，证明了Src在维持上皮完整性中的关键作用。
