[p120连环蛋白缺失改变人肺癌细胞中小GTP酶的活性。]
[Ablation of p120-Catenin Altering the Activity of Small GTPase in Human Lung Cancer Cells.].
作者信息
Liu Shuli, Liu Yang, Liu Nan, Wang Enhua
机构信息
Department of Pathology, College of Basic Medical Sciences, China Medical University and Department of Pathology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China.
出版信息
Zhongguo Fei Ai Za Zhi. 2009 May 20;12(5):369-74. doi: 10.3779/j.issn.1009-3419.2009.05.002.
BACKGROUND
p120-catenin (p120(ctn)), a member of the Armadillo gene family, has emerged as an important modulator of small GTPase activities. Therefore, it plays novel roles in tumor malignant phenotype, such as invasion and metastasis, whose mechanism are not well clarified yet. The aim of this study is to explore the roles of p120ctn on the regulation of small GTP family members in lung cancer and the effects to lung cancer invasions and metastasis.
METHODS
After p120(ctn) was knocked down by siRNA, in vivo and in vitro analysis was applied to investigate the role and possible mechanism of p120(ctn) in lung cancer, such as Western Blot, pull-down analysis, and nude mice models.
RESULTS
p120(ctn) depletion inactivated RhoA, with the the activity of Cdc42 and Rac1 increased, the invasiveness of lung cancer cells was promoted both in vitro and in vivo.
CONCLUSIONS
p120(ctn) gene knockdown enhances the metastasis of lung cancer cells, probably by altering expression of small GTPase, such as inactivation of RhoA and activation of Cdc42/Rac1.
背景
p120连环蛋白（p120(ctn)）是犰狳基因家族的成员，已成为小GTP酶活性的重要调节因子。因此，它在肿瘤恶性表型中发挥新的作用，如侵袭和转移，但其机制尚未完全阐明。本研究的目的是探讨p120ctn在肺癌中对小GTP家族成员的调节作用以及对肺癌侵袭和转移的影响。
方法
用小干扰RNA敲低p120(ctn)后，采用体内和体外分析方法，如蛋白质免疫印迹法、下拉分析和裸鼠模型，研究p120(ctn)在肺癌中的作用及可能机制。
结果
p120(ctn)缺失使RhoA失活，Cdc42和Rac1活性增加，体外和体内肺癌细胞的侵袭性均增强。
结论
p120(ctn)基因敲低增强肺癌细胞的转移，可能是通过改变小GTP酶的表达，如RhoA失活和Cdc42/Rac1激活。
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