我们发现肺癌细胞中p120ctn-1能够上调E-cad表达并降低肺癌细胞侵袭能力；而p120ctn-3虽不能调节E-cad表达，但能上调Kaiso下游靶基因的表达，增强肺癌细胞的侵袭能力。已知p120ctn与E-cad或与Kaiso的结合位点相同，我们推测p120ctn-1上的螺旋卷曲结构调节了其与E-cad的结合并抑制了其与Kaiso的结合，而p120ctn-3由于缺少螺旋卷曲结构故只能与Kaiso结合，从而使二者对细胞的侵袭能力起到了不同的调节作用。本研究拟构建并转染p120ctn-1,3及多种p120ctn剪切体质粒，双向调控其表达，应用WB、免疫共沉淀及免疫共聚焦等方法，检测p120ctn-1、-3与E-cad、Kaiso结合、定位及对Kaiso下游靶基因表达的影响，并经体内外实验,揭示p120ctn-1和-3对肺癌细胞生物学行为不同影响的机制，为肺癌的防治提供新的理论和实验基础。

Our previous studies have shown that p120-catenin isoform 1 (p120ctn-1) could reduce the cell invasiveness by up-regulating the expression of E-cadherin. P120ctn isoform 3(p120ctn-3) could enhance the cell invasiveness by up-regulating the expression of the downstream target genes of Kaiso, with no effect on E-cadherin expression. It has been reported that the binding sites mediating the interaction of p120ctn with E-cadherin or Kaiso are both located in the 1-7 armadillo repeats of p120ctn, and the coiled-coil domain in the amino-terminal of p120ctn-1 may participate in protein-protein interactions. We hypothesize that the coiled-coil domain of p120ctn-1 can facilitate the interaction of p120ctn-1 with E-cadherin and reduce the cell invasiveness; p120ctn-3, which lacks the coiled-coil domain, can interact with Kaiso and enhance the cell invasiveness. In the current study, we will screen and select 4 lung cance cell lines, and knockdown p120ctn with small interfering RNA. P120ctn-1, -3 or deletion mutants will be restituted in the cells to investigate the interactions of p120ctn with E-cadherin or Kaiso, the localation of E-cadherin and Kaiso,and the expression of the downstream target genes of Kaiso using Western Blot, co-immunoprecipitation, confocal immunofluorescence microscopy. We will try to clarify the different mechanisms by which p120ctn-1 and -3 affect the biological behaviors of lung cancer cell. The results of this study can provide new ideas and experimental basis for the prevention and treatment of lung cancer.