Liu Xin, Chu Kent-Man
Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
Biomed Res Int. 2014;2014:637308. doi: 10.1155/2014/637308. Epub 2014 Aug 12.
E-cadherin (epithelial-cadherin), encoded by the CDH1 gene, is a transmembrane glycoprotein playing a crucial role in maintaining cell-cell adhesion. E-cadherin has been reported to be a tumor suppressor and to be down regulated in gastric cancer. Besides genetic mutations in CDH1 gene to induce hereditary diffuse gastric cancer (HDGC), epigenetic factors such as DNA hypermethylation also contribute to the reduction of E-cadherin in gastric carcinogenesis. In addition, expression of E-cadherin could be mediated by infectious agents such as H. pylori (Helicobacter pylori). As E-cadherin is vitally involved in signaling pathways modulating cell proliferation, survival, invasion, and migration, dysregulation of E-cadherin leads to dysfunction of gastric epithelial cells and contributes to gastric cancer development. Moreover, changes in its expression could reflect pathological conditions of gastric mucosa, making its role in gastric cancer complicated. In this review, we summarize the functions of E-cadherin and the signaling pathways it regulates. We aim to provide comprehensive perspectives in the molecular mechanism of E-cadherin and its involvement in gastric cancer initiation and progression. We also focus on its applications for early diagnosis, prognosis, and therapy in gastric cancer in order to open new avenues in this field.
E-钙黏蛋白(上皮钙黏蛋白)由CDH1基因编码,是一种跨膜糖蛋白,在维持细胞间黏附中起关键作用。据报道,E-钙黏蛋白是一种肿瘤抑制因子,在胃癌中表达下调。除了CDH1基因的基因突变可诱发遗传性弥漫性胃癌(HDGC)外,DNA高甲基化等表观遗传因素也在胃癌发生过程中导致E-钙黏蛋白减少。此外,E-钙黏蛋白的表达可由幽门螺杆菌等感染因子介导。由于E-钙黏蛋白在调节细胞增殖、存活、侵袭和迁移的信号通路中至关重要,其失调会导致胃上皮细胞功能障碍,并促进胃癌的发展。此外,其表达变化可反映胃黏膜的病理状况,使其在胃癌中的作用变得复杂。在本综述中,我们总结了E-钙黏蛋白的功能及其调节的信号通路。我们旨在全面阐述E-钙黏蛋白的分子机制及其在胃癌发生和发展中的作用。我们还关注其在胃癌早期诊断、预后和治疗中的应用,以便在该领域开辟新途径。