Ablation of p120-catenin enhances invasion and metastasis of human lung cancer cells
Ablation of p120-catenin enhances invasion and metastasis of human lung cancer cells
复制标题
p120-连环蛋白的消除增强人肺癌细胞的侵袭和转移
DOI：
10.1111/j.1349-7006.2008.01067.x
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发表时间：
2009-03-01
期刊：
影响因子：
5.7
通讯作者：
Wang, En-Hua
中科院分区：
文献类型：
--
作者：
Liu, Yang;Li, Qing-Chang;Wang, En-Hua
P120-catenin是Armadillo基因家族中的一员，既是钙粘附素稳定性的主要调节因子，也是小GTP酶活性的重要调节器。因此，它在肿瘤的侵袭和转移等恶性表型中发挥着新的作用。我们已经报道，p120-catenin的异常表达与肺鳞癌(SCC)和腺癌的淋巴结转移有关。为了探讨p120-catenin在肺癌中的作用和可能的机制，我们用小干扰RNA(SiRNA)敲除了p120-catenin。我们发现，去除p120-catenin可降低E-钙粘蛋白和β-catenin蛋白的水平，以及β-catenin的mRNA水平。此外，p120-catenin耗竭使RhoA失活，但使CDC42和rac1活性增强，并促进肺癌细胞的增殖和体内侵袭能力。我们的数据显示，p120-catenin基因敲除增强了肺癌细胞的转移，可能是通过降低E-钙粘素和β-catenin水平而抑制细胞与细胞的黏附，或者改变小GTP酶的活性，如RhoA失活和CDc42/rac1的激活。(《癌症科学》2009；100：441-448)。
p120-catenin, a member of the Armadillo gene family, has emerged as both a master regulator of cadherin stability and an important modulator of small GTPase activities. Therefore, it plays novel roles in tumor malignant phenotype, such as invasion and metastasis. We have reported previously that abnormal expression of p120-catenin is associated with lymph node metastasis in lung squamous cell carcinomas (SCC) and adenocarcinomas. To investigate the role and possible mechanism of p120-catenin in lung cancer, we knocked down p120-catenin using small interfering RNA (siRNA). We found that ablation of p120-catenin reduced the levels of E-cadherin and beta-catenin proteins, as well as the mRNA of beta-catenin. Furthermore, p120-catenin depletion inactivated RhoA, but increased the activity of Cdc42 and Rac1, and promoted proliferation and the invasive ability of lung cancer cells both in vitro and in vivo. Our data reveal that p120-catenin gene knockdown enhances the metastasis of lung cancer cells, probably by either depressing cell-cell adhesion due to lower levels of E-cadherin and beta-catenin, or altering the activity of small GTPase, such as inactivation of RhoA and activation of Cdc42/Rac1. (Cancer Sci 2009; 100: 441-448).