Department of Small Animal Diseases, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.
Department of Pathology and Veterinary Diagnostics, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.
Int J Mol Sci. 2020 Oct 15;21(20):7624. doi: 10.3390/ijms21207624.
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.
钙黏蛋白在组织稳态中发挥着重要作用,因为它们在胚胎发生、组织形态发生、分化和癌变过程中负责细胞间的黏附。钙黏蛋白与连环蛋白不可分割地连接,形成钙黏蛋白-连环蛋白复合物,这对于细胞间黏附至关重要。钙黏蛋白-连环蛋白复合物的任何功能障碍或不稳定性都可能导致肿瘤进展。上皮间质转化(EMT)是一种机制,在此机制中,上皮钙黏蛋白(E-cadherin)在肿瘤进展过程中丢失。然而,在肿瘤发生过程中,有许多过程发生,E-cadherin、核β-catenin 和 p120 连环蛋白(p120)信号的下调是最关键的。其他信号通路,如受体酪氨酸激酶(RTK)、Rho GTPases、磷酸肌醇 3-激酶(PI3K)和 Hippo,影响钙黏蛋白的细胞间黏附,也有助于肿瘤的进展和转移。在肿瘤发生过程中可能会激活许多信号通路;因此,针对钙黏蛋白的药物似乎可以限制恶性肿瘤的进展。本文讨论了钙黏蛋白在涉及肿瘤生长的选定信号机制中的作用。还将讨论钙黏蛋白在人类和动物癌症中的临床重要性。