Liu Yang, Dong Qian-Ze, Zhao Yue, Dong Xin-Jun, Miao Yuan, Dai Shun-Dong, Yang Zhi-Qiang, Zhang Di, Wang Yan, Li Qing-Chang, Zhao Chen, Wang En-Hua
Department of Pathology, College of Basic Medical Sciences, China Medical University and Department of Pathology, First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Exp Cell Res. 2009 Mar 10;315(5):890-8. doi: 10.1016/j.yexcr.2008.12.016. Epub 2009 Jan 3.
Different isoforms of p120-catenin (p120ctn), a member of the Armadillo gene family, are variably expressed in different tissues as a result of alternative splicing and the use of multiple translation initiation codons. When expressed in cancer cells, these isoforms may confer different properties with respect to cell adhesion and invasion. We have previously reported that the p120ctn isoforms 1 and 3 were the most highly expressed isoforms in normal lung tissues, and their expression level was reduced in lung tumor cells. To precisely define their biological roles, we transfected p120ctn isoforms 1A and 3A into the lung cancer cell lines A549 and NCI-H460. Enhanced expression of p120ctn isoform 1A not only upregulated E-cadherin and beta-catenin, but also downregulated the Rac1 activity, and as a result, inhibited the ability of cells to invade. In contrast, overexpression of p120ctn isoform 3A led to the inactivation of Cdc42 and the activation of RhoA, and had a smaller influence on invasion. However, we found that isoform 3A had a greater ability than isoform 1A in both inhibiting the cell cycle and reducing tumor cell proliferation. The present study revealed that p120ctn isoforms 1A and 3A differently regulated the adhesive, proliferative, and invasive properties of lung cancer cells through distinct mechanisms.
犰狳基因家族成员p120连环蛋白（p120ctn）的不同异构体，由于可变剪接和多个翻译起始密码子的使用，在不同组织中呈现出不同的表达水平。当在癌细胞中表达时，这些异构体在细胞黏附和侵袭方面可能具有不同的特性。我们之前报道过，p120ctn异构体1和3是正常肺组织中表达最高的异构体，而它们在肺肿瘤细胞中的表达水平降低。为了精确确定它们的生物学作用，我们将p120ctn异构体1A和3A转染到肺癌细胞系A549和NCI-H460中。p120ctn异构体1A的表达增强不仅上调了E-钙黏蛋白和β-连环蛋白，还下调了Rac1活性，结果抑制了细胞的侵袭能力。相反，p120ctn异构体3A的过表达导致Cdc42失活和RhoA激活，对侵袭的影响较小。然而，我们发现异构体3A在抑制细胞周期和减少肿瘤细胞增殖方面比异构体1A具有更强的能力。本研究表明，p120ctn异构体1A和3A通过不同机制对肺癌细胞的黏附、增殖和侵袭特性进行不同的调控。
