钙粘蛋白在组织稳态中起重要作用,因为它们在胚胎发育过程中负责细胞间的粘附,组织形态发生,分化和致癌作用。钙黏着蛋白与连环蛋白密不可分,形成钙粘蛋白-连环蛋白复合物,这对细胞间粘附至关重要。钙粘蛋白-连环蛋白复合物的任何功能障碍或不稳定都可能导致肿瘤进展。上皮间充质转化(EMT)是上皮钙粘蛋白(E-cadherin)表达在肿瘤进展过程中丢失的机制。然而,在肿瘤发生过程中,发生了许多过程,和E-cadherin的下调,核β-连环蛋白和p120连环蛋白(p120)信号是最关键的。其他信号通路,如受体酪氨酸激酶(RTK),RhoGTPases,磷酸肌醇3-激酶(PI3K)和Hippo影响钙粘蛋白细胞间的粘附,也有助于肿瘤进展和转移。许多信号通路可能在肿瘤发生过程中被激活;因此,钙粘蛋白靶向药物似乎限制了恶性肿瘤的进展。这篇综述讨论了钙黏着蛋白在参与肿瘤生长的选定信号机制中的作用。钙黏着蛋白的临床重要性将在人类和动物癌症的病例中讨论。
Cadherins play an important role in tissue homeostasis, as they are responsible for cell-cell adhesion during embryogenesis, tissue morphogenesis, differentiation and carcinogenesis. Cadherins are inseparably connected with catenins, forming
cadherin-catenin complexes, which are crucial for cell-to-cell adherence. Any dysfunction or destabilization of
cadherin-catenin complex may result in tumor progression. Epithelial mesenchymal transition (EMT) is a mechanism in which epithelial
cadherin (E-
cadherin) expression is lost during tumor progression. However, during tumorigenesis, many processes take place, and downregulation of E-cadherin, nuclear β-catenin and p120 catenin (p120) signaling are among the most critical. Additional signaling pathways, such as Receptor tyrosine kinase (RTK), Rho GTPases, phosphoinositide 3-kinase (PI3K) and Hippo affect cadherin cell-cell adhesion and also contribute to tumor progression and metastasis. Many signaling pathways may be activated during tumorigenesis; thus, cadherin-targeting drugs seem to limit the progression of malignant tumor. This
review discusses the role of cadherins in selected signaling mechanisms involved in tumor growth. The clinical importance of
cadherin will be discussed in cases of human and animal cancers.