Molecular and Cellular Oncology Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium.
Cold Spring Harb Perspect Biol. 2009 Dec;1(6):a003129. doi: 10.1101/cshperspect.a003129. Epub 2009 Sep 23.
We review the role of cadherins and cadherin-related proteins in human cancer. Cellular and animal models for human cancer are also dealt with whenever appropriate. E-cadherin is the prototype of the large cadherin superfamily and is renowned for its potent malignancy suppressing activity. Different mechanisms for inactivating E-cadherin/CDH1 have been identified in human cancers: inherited and somatic mutations, aberrant protein processing, increased promoter methylation, and induction of transcriptional repressors such as Snail and ZEB family members. The latter induce epithelial mesenchymal transition, which is also associated with induction of "mesenchymal" cadherins, a hallmark of tumor progression. VE-cadherin/CDH5 plays a role in tumor-associated angiogenesis. The atypical T-cadherin/CDH13 is often silenced in cancer cells but up-regulated in tumor vasculature. The review also covers the status of protocadherins and several other cadherin-related molecules in human cancer. Perspectives for emerging cadherin-related anticancer therapies are given.
我们回顾了钙黏蛋白及其相关蛋白在人类癌症中的作用。只要合适，我们还会涉及针对人类癌症的细胞和动物模型。E-钙黏蛋白是大型钙黏蛋白超家族的原型，因其强大的抑癌活性而闻名。在人类癌症中，已经确定了使 E-钙黏蛋白/CDH1 失活的不同机制：遗传和体细胞突变、异常蛋白加工、启动子甲基化增加，以及诱导转录抑制因子，如 SNAIL 和 ZEB 家族成员。后者诱导上皮间质转化，这也与“间质”钙黏蛋白的诱导有关，是肿瘤进展的标志。VE-钙黏蛋白/CDH5 在肿瘤相关血管生成中发挥作用。非典型 T-钙黏蛋白/CDH13 在癌细胞中通常被沉默，但在肿瘤血管中上调。该综述还涵盖了原钙黏蛋白和其他几种钙黏蛋白相关分子在人类癌症中的状态。还给出了新兴的钙黏蛋白相关抗癌疗法的前景。
