中文摘要：

背景与目的作为catenin蛋白家族的重要成员之一,p120-catenin（p120ctn）是small GTPase酶的重要调节因子,影响细胞的运动能力,但其中具体的调节机制尚不清楚。本研究旨在探讨p120ctn在肺癌细胞系中对small GTP酶家族核心成员的调节作用,及其对肺癌细胞侵袭、转移的影响。方法应用siRNA方法成功地建立了p120ctn基因沉默的多种癌细胞系BE1、SPC、LTE的细胞克隆,采用Western Blot,pull-down蛋白活性分析,裸鼠移植等体内外实验探讨其可能的调节机制。结果p120ctn的基因沉默能激活Cdc42和Rac1,失活RhoA,并且在活体内外促进肺癌细胞的侵袭和转移。结论p120ctn的缺失可激活Cdc42/Rac1、失活RhoA,促进肺癌细胞的侵袭和转移能力。

英文摘要：

Background and objective pl20-catenin （p120^ctn）, a member of the Armadillo gene family, has emerged as an important modulator of small C,,TPase 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 p120^ctn 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 Racl increased, the invasiveness of lung cancer cells was promoted both in vitro and in vivo. Conclusion 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 Cde42/ Rac 1.