IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto , Rua Dr. Roberto Frias s/n, 4200-465 Porto , Portugal +00351 225570700 ; +00351 225570799 ;
Expert Opin Ther Targets. 2013 Oct;17(10):1187-201. doi: 10.1517/14728222.2013.827174. Epub 2013 Aug 19.
Epithelial cadherin (E-cadherin) plays a key role in epithelial cell-cell adhesion, contributing to tissue differentiation and homeostasis. Throughout the past decades, research has shed light on the molecular mechanisms underlying E-cadherin's role in tumor progression, namely in invasion and metastization. Emerging evidence established E-cadherin as a tumor suppressor and suggests that targeting E-cadherin or downstream signaling molecules may constitute effective cancer therapeutics.
This review aims to cover E-cadherin-mediated signaling during cancer development and progression and highlight putative therapeutic targets.
Reconstitution of E-cadherin expression or targeting of E-cadherin downstream molecules holds promise in cancer therapies. Considering the high frequency of CDH1 promoter hypermethylation as a second hit in malignant lesions from hereditary diffuse gastric cancer patients, histone deacetylase inhibitors are potential therapeutic agents in combination with conventional chemotherapy, specifically in initial tumor stages. Concerning E-cadherin-mediated signaling, we propose that HER receptors (as epidermal growth factor receptor) and Notch downstream targets are clinically relevant and should be considered in gastric cancer therapeutics and control.
上皮钙黏蛋白（E-cadherin）在细胞间黏附中起着关键作用，有助于组织分化和稳态。在过去的几十年中，研究揭示了 E-cadherin 在肿瘤进展中，特别是在侵袭和转移中的作用的分子机制。新出现的证据将 E-cadherin 确立为一种肿瘤抑制因子，并表明针对 E-cadherin 或下游信号分子可能构成有效的癌症治疗方法。
本综述旨在涵盖癌症发生和发展过程中 E-cadherin 介导的信号转导，并强调潜在的治疗靶点。
E-cadherin 表达的重建或针对 E-cadherin 下游分子的靶向治疗在癌症治疗中具有潜力。考虑到遗传性弥漫性胃癌患者恶性病变中 CDH1 启动子超甲基化作为二次打击的高频率，组蛋白去乙酰化酶抑制剂与传统化疗联合使用具有潜在的治疗作用，特别是在肿瘤早期阶段。关于 E-cadherin 介导的信号转导，我们提出 HER 受体（如表皮生长因子受体）和 Notch 下游靶标具有临床相关性，应在胃癌治疗和控制中考虑。
