Li Chao, Ao Hongfeng, Chen Guofang, Wang Fang, Li Fang
Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Pathology, Shanghai Fengxian District Central Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai, China.
Front Oncol. 2020 Jan 9;9:1481. doi: 10.3389/fonc.2019.01481. eCollection 2019.
Cancer-associated cadherin 20 (CDH20) is a novel identified cadherin that is genetically altered in several types of human cancer, including cervical cancer. However, its involvement in the progression of cervical cancer remains unknown. In this study, we show that CDH20 was downregulated in clinical cervical cancer samples and its expression correlated with cervical cancer clinical features. CDH20 negatively regulated the migration and invasion of cervical cancer cells. CDH20 increased the expression and promoted the cytoplasm and membrane translocation of β-catenin, and interacted with β-catenin. Mechanistically, CDH20/β-catenin suppressed transforming growth factor-β (TGF-β)-induced epithelial-to-mesenchymal transition (EMT) by downregulating Snail through reducing the phosphorylation and nuclear translocation of Smad2/3. Taken together, our data suggest that CDH20 may act as a tumor suppressor that interacts with β-catenin to inhibit cervical cancer cell migration and invasion via TGF-β/Smad/Snail mediated EMT.
癌症相关钙黏蛋白20（CDH20）是一种新发现的钙黏蛋白，在包括宫颈癌在内的多种人类癌症中发生基因改变。然而，其在宫颈癌进展中的作用尚不清楚。在本研究中，我们发现CDH20在临床宫颈癌样本中表达下调，且其表达与宫颈癌临床特征相关。CDH20负向调节宫颈癌细胞的迁移和侵袭。CDH20增加β-连环蛋白的表达并促进其向细胞质和细胞膜的转位，并与β-连环蛋白相互作用。机制上，CDH20/β-连环蛋白通过降低Smad2/3的磷酸化和核转位来下调Snail，从而抑制转化生长因子-β（TGF-β）诱导的上皮-间质转化（EMT）。综上所述，我们的数据表明，CDH20可能作为一种肿瘤抑制因子，与β-连环蛋白相互作用，通过TGF-β/Smad/Snail介导的EMT抑制宫颈癌细胞的迁移和侵袭。
