van Roy F, Berx G
Department for Molecular Biomedical Research, Molecular Cell Biology Unit, VIB, Technologiepark 927, 9052 Ghent, Belgium.
Cell Mol Life Sci. 2008 Nov;65(23):3756-88. doi: 10.1007/s00018-008-8281-1.
This review is dedicated to E-cadherin, a calcium-dependent cell-cell adhesion molecule with pivotal roles in epithelial cell behavior, tissue formation, and suppression of cancer. As founder member of the cadherin superfamily, it has been extensively investigated. We summarize the structure and regulation of the E-cadherin gene and transcript. Models for E-cadherin-catenin complexes and cell junctions are presented. The structure of the E-cadherin protein is discussed in view of the diverse functions of this remarkable protein. Homophilic and heterophilic adhesion are compared, including the role of E-cadherin as a receptor for pathogens. The complex post-translational processing of E-cadherin is reviewed, as well as the many signaling activities. The role of E-cadherin in embryonic development and morphogenesis is discussed for several animal models. Finally, we review the multiple mechanisms that disrupt E-cadherin function in cancer: inactivating somatic and germline mutations, epigenetic silencing by DNA methylation and epithelial to mesenchymal transition-inducing transcription factors, and dysregulated protein processing.
本综述聚焦于E-钙黏蛋白,一种钙依赖性细胞间黏附分子,在上皮细胞行为、组织形成及癌症抑制中发挥关键作用。作为钙黏蛋白超家族的创始成员,它已得到广泛研究。我们总结了E-钙黏蛋白基因和转录本的结构与调控。介绍了E-钙黏蛋白-连环蛋白复合物及细胞连接的模型。鉴于这种非凡蛋白质的多种功能,对E-钙黏蛋白的结构进行了讨论。比较了同嗜性和异嗜性黏附,包括E-钙黏蛋白作为病原体受体的作用。综述了E-钙黏蛋白复杂的翻译后加工过程以及众多信号传导活性。针对多种动物模型讨论了E-钙黏蛋白在胚胎发育和形态发生中的作用。最后,我们综述了癌症中破坏E-钙黏蛋白功能的多种机制:体细胞和种系失活突变、DNA甲基化导致的表观遗传沉默以及上皮-间质转化诱导转录因子,以及蛋白质加工失调。