CDH1
小结
CDH1是抑癌基因，CDH1编码蛋白(E-cadherin)是一种钙依赖性跨膜糖蛋白，主要在上皮细胞中表达，在细胞-细胞粘附、信号级联和上皮-间质转化（EMT）中起作用。E-cadherin胞外部分通过与相邻细胞上的钙粘蛋白结合而促进同种细胞间粘附，而胞内结构域通过与连环蛋白的相互作用与肌动蛋白细胞骨架连接，并起到激活在EMT中起作用的信号级联的功能。转录因子SNAIL是胚胎发育期间EMT的关键调节因子，抑制肿瘤细胞系中E-cadherin基因的表达。E-cadherin功能/表达的缺乏通过改变细胞形态、降低细胞粘附和增加细胞运动而促进了癌症进展。伴随点突变和杂合性缺失（LOH），CDH1启动子的过甲基化引起的表观遗传沉默与癌症进展过程中的E-cadherin基因表达缺失有关。携带胚系CDH1致病突变的个体发展成弥漫性胃癌和乳腺癌的风险增加。E-cadherin的缺失突变也被证明在多种散发性癌症类型中检测到，包括胃癌、结直肠癌和食管癌。
CDH1, also known as E-cadherin, is a calcium-dependent transmembrane glycoprotein that is mainly expressed in epithelial cells and functions in cell-cell adhesion, signaling cascades and epithelial-to-mesenchymal transition (EMT). The extracellular portion of E-cadherin facilitates homophilic cell-to-cell adhesion by binding to cadherins on adjacent cells, while the intracellular domain is tethered to the actin cytoskeleton through interactions with catenins and functions to activate signaling cascades that play a role in the EMT. The transcription factor SNAIL, a key regulator of the EMT during embryonic development, represses expression of the E-cadherin gene in tumor cell lines. Lack of E-cadherin function/expression enables cancer progression by altering cellular morphology, decreasing cellular adhesion, and increasing cellular motility. Along with point mutations and loss of heterozygosity (LOH), epigenetic silencing by hypermethylation of the CDH1 promoter has been associated with the loss of E-cadherin gene expression during cancer progression. Individuals with a germline CDH1 mutation have an increased risk of developing diffuse gastric cancer and breast cancer. Loss of E-cadherin has also been demonstrated in a variety of sporadic cancer types including gastric cancer, colorectal cancer, and esophageal cancer.