细胞极性机制及细胞粘附控制上皮细胞的"门户"功能。如果参与细胞极性形成的基因表达改变，导致其编码蛋白的表达及定位改变，可使上皮细胞失去极性及细胞间粘附，而具有间质细胞的形态、特性及获得游走、迁移的能力，即EMT。RTK介导的信号通路激活、细胞粘附改变及Rho家族小GTP酶激活均参与此过程。目前，极性相关分子调控细胞转化的机制不清。我们前期的研究提示，LAP蛋白家族的新成员Erbin可能在上述过程中发挥重要的作用；在肿瘤细胞中Erbin的水平明显降低，敲低Erbin表达可显著促进裸鼠体内移植瘤生长，并导致肿瘤严重的腹腔种植转移，提示Erbin在EMT及肿瘤发生中行使重要的功能。本研究拟在前期基础上，深入探索Erbin在细胞粘附、细胞极性复合物形成及细胞转化中的调控作用，阐释相关的分子机制，揭示极性蛋白与原癌蛋白互作在维持上皮细胞内环境稳定中的意义，鉴定Erbin作为新的抑癌基因的可能性。

The mechanisms of cell polarity and cell-cell adhesion regulate the gate and fence function of epithelial cells. However, the alterations in the expression and subcellular localization of the polarity-related proteins will result in loss of cell polarity and cell-cell adhesion in epithelial cells, which then display the morphology of mesenchymal cells and gain the potential of motility and migration, that is epithelial-mesenchymal transition (EMT). The processes are involved in induction of receptor tyrosine kinase-mediated signal transduction pathways, changes in celll adhesion and the activation of small GTPases of the Rho family. The mechanisms underlying regulation of cell transformation by polarity-related molecules are unclear. Our previous studies suggested that Erbin, a recently identified new member of LAP protein family plays very important roles in these processes. In tumor cells, the level of Erbin is significantly decreased. Knock-down of Erbin expression greatly promotes tumor growth in nude mice and leads to severe intraperitoneal metastases, implicating that Erbin exerts critical functions in tumor development and progression. This project will explore the roles of Erbin in cell adhesion, assembly of a cell polarity complex and cell transformation, elucidate the related molecular mechanisms, reveal the significance of the interaction between polarity proteins and oncoproteins in maintaining cell polarity and investigate the possibility of Erbin as a putative tumor suppressor.