P120-catenin isoforms 1A and 3A differently affect invasion and proliferation of lung cancer cells
P120-catenin isoforms 1A and 3A differently affect invasion and proliferation of lung cancer cells
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P120-catenin亚型1A和3A对肺癌细胞侵袭和增殖的影响不同
DOI：
10.1016/j.yexcr.2008.12.016
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发表时间：
2009-03-10
影响因子：
3.7
通讯作者：
Wang, En-Hua
中科院分区：
文献类型：
--
作者：
Liu, Yang;Dong, Qian-Ze;Wang, En-Hua
p120-catenin（p120 ctn）是Armadillo基因家族的一员，由于选择性剪接和使用多个翻译起始密码子，p120-catenin的不同亚型在不同组织中不同程度地表达。当在癌细胞中表达时，这些同种型可赋予关于细胞粘附和侵袭的不同性质。我们以前曾报道过，p120 ctn亚型1和3是在正常肺组织中表达最高的亚型，其表达水平在肺肿瘤细胞中降低。为了精确定义它们的生物学作用，我们将p120 ctn亚型1A和3A转染到肺癌细胞系A549和NCI-H460中。p120 ctn亚型1A的表达增强不仅上调了E-cadherin和beta-catenin的表达，而且下调了Rac 1的活性，从而抑制了细胞的侵袭能力。而p120 ctn亚型3A的过表达导致Cdc 42的失活和RhoA的激活，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IA具有更大的能力。目前的研究表明，p120 ctn亚型1A和3A不同调节肺癌细胞的粘附，增殖和侵袭特性，通过不同的机制。(C)2008年爱思唯尔公司All rights reserved.
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 I A 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. (C) 2008 Elsevier Inc. All rights reserved.