The tumor-suppressor function of E-cadherin
The tumor-suppressor function of E-cadherin
复制标题
DOI：
10.1086/302173
复制
发表时间：
1998-12-01
影响因子：
9.8
通讯作者：
Christofori, G
中科院分区：
文献类型：
--
作者：
Semb, H;Christofori, G
从良性肿瘤到侵袭性、转移性癌细胞的转变涉及细胞外基质环境、细胞运动性和细胞-细胞粘附的变化。由于细胞-细胞粘附分子在人类癌变过程中受到动态调节，因此它们与肿瘤发生有关，特别是在肿瘤进展的后期阶段，即肿瘤细胞侵袭和转移（Thiery 1996）。在这篇综述中，我们集中在遗传学和细胞培养研究的证据，支持的功能性作用的E-钙粘蛋白/连环蛋白粘附复合物在致癌。我们讨论了两个潜在的下游信号，在E-钙粘蛋白介导的细胞-细胞粘附的变化可能会引起在肿瘤发生和E-钙粘蛋白功能和Wnt信号之间的可能连接。许多研究表明，E-钙粘蛋白与人类癌症的发展有关。对这种蛋白质的巨大兴趣可能部分反映了它作为上皮细胞中主要细胞粘附分子的作用，上皮细胞是80%的人类癌症的来源。上皮细胞通过连接复合体紧密连接，连接复合体由紧密连接、粘附连接和桥粒组成，桥粒是与肌动蛋白和中间细胞骨架丝系统密切相关的结构。E-钙粘蛋白作为粘附连接中的主要粘附受体，介导Ca 2+依赖的嗜同性相互作用。该功能对于建立和维持细胞-细胞连接至关重要（Takeichi 1995; Aberle et al. 1996综述），E-钙粘蛋白缺陷的小鼠在子宫内死亡，因为第一上皮（滋养外胚层）的形成缺陷（Larue et al. 1994; Riethmacher et al. 1995）。在细胞内，E-钙粘蛋白与连环蛋白（a-、B-和g-连环蛋白/斑珠蛋白）连接，后者将E-钙粘蛋白与肌动蛋白细胞骨架连接（图1）。失败也
The transition from benign tumors to invasive, metastatic cancer cells involves changes in the extracellular matrix environment, cell motility, and cell-cell adhesion. Because cell-cell–adhesion molecules are dynamically regulated during human carcinogenesis, they have been implicated in tumorigenesis, especially during the later stages of tumor progression—that is, tumor-cell invasion and metastasis (Thiery 1996). In this review, we focus on the evidence from genetics and cell-culture studies that support a functional role of E-cadherin/catenin adhesion complexes in carcinogenesis. We discuss both the potential downstream signals that changes in E-cadherin–mediated cell-cell adhesion may elicit during tumorigenesis and a possible connection between E-cadherin function and Wnt signaling. Many studies have implicated E-cadherin in the development of human cancers. The great interest in this protein may, in part, reflect its role as the major cellcell–adhesion molecule in epithelial cells, the cell type from which∼ 80% of human cancers derive. Epithelial cells are tightly interconnected through a junctional complex, consisting of tight junctions, adherens junctions, and desmosomes, structures that are intimately associated with the actin and intermediate cytoskeletal filament systems. E-cadherin mediates Ca2+-dependent homophilic interactions, as the major adhesion receptor in adherens junctions. This function is essential both to establish and to maintain cell-cell junctions (reviewed in Takeichi 1995; Aberle et al. 1996), and mice deficient for E-cadherin die in utero, because of defective formation of the first epithelium, the trophectoderm (Larue et al. 1994; Riethmacher et al. 1995). Intracellularly, E-cadherin is linked to the catenins (a-, b-, and g-catenin/plakoglobin), which connect E-cadherin to the actin cytoskeleton (fig. 1). Failure either