Cooperation between snail and LEF-1 transcription factors is essential for TGF-β1-induced epithelial-mesenchymal transition
Cooperation between snail and LEF-1 transcription factors is essential for TGF-β1-induced epithelial-mesenchymal transition
复制标题
DOI：
10.1091/mbc.e05-08-0767
复制
发表时间：
2006-04-01
影响因子：
3.3
通讯作者：
Goodenough, DA
中科院分区：
文献类型：
--
作者：
Medici, D;Hay, ED;Goodenough, DA
转化生长因子β1(TGF-β1)可在胚胎发育和疾病进展的不同阶段诱导上皮-间充质转化(EMT)。这种细胞形态的改变通常以细胞极性的改变和黏附蛋白的丢失为特征，如E-钙粘附素。在这里，我们证明了EMT与MDCKII细胞暴露于转化生长因子-β1后72小时内claudin-1、claudin-2、occludin和E-cadherin的表达缺失有关。有研究表明，这种表达缺失是通过转化生长因子-β1以一种不依赖于Smad的机制发生的，涉及MEK和PI3K途径，这两个途径先前已被证明诱导Snail(Snai-1)基因的表达。在这里，我们表明，这些途径负责紧密连接的丢失和E-钙粘附素的部分丢失。然而，我们的结果也表明，E-钙粘附素的完全丧失和向间充质表型的转化依赖于Smad信号，Smad信号随后刺激β-连环蛋白/Lef-1复合体的形成，从而诱导EMT。
Transforming growth factor beta 1 (TGF-beta 1) has been shown to induce epithelial-mesenchymal transition (EMT) during various stages of embryogenesis and progressive disease. This alteration in cellular morphology is typically characterized by changes in cell polarity and loss of adhesion proteins such as E-cadherin. Here we demonstrate that EMT is associated with loss of claudin-1, claudin-2, occludin, and E-cadherin expression within 72 h of exposure to TGF-beta 1 in MDCKII cells. It has been suggested that this expression loss occurs through TGF-beta 1 in a Smad-independent mechanism, involving MEK and PI3K pathways, which have previously been shown to induce expression of the Snail (SNAI-1) gene. Here we show that these pathways are responsible for loss of tight junctions and a partial loss of E-cadherin. However, our results also demonstrate that a complete loss of E-cadherin and transformation to the mesenchymal phenotype are dependent on Smad signaling, which subsequently stimulates formation of beta-catenin/LEF-1 complexes that induce EMT.