结肠癌的侵袭转移是导致结肠癌不良预后的主要原因。我们前期研究发现：①蛋白磷酸酶PP4C在结肠癌中呈高表达，其通过调控肿瘤的侵袭转移，反应不良预后；②高通量蛋白质组筛选PP4C相互作用的蛋白，发现PP4C可以与转录因子Prox1相互作用，形成PP4C/Prox1复合体；③高通量表达谱芯片筛选结果提示，PP4C和Prox1都可以调控IGF1R基因的转录，活化IGF1R通路，影响结肠癌细胞的侵袭转移。由此提出“PP4C/Prox1-IGF1R”通路在结肠癌中的存在，并调控结肠癌侵袭转移，影响不良预后。本项目拟围绕此信号通路开展以下研究：①分析PP4C、Prox1和IGF1R之间的关系，对此信号通路进行生化与分子细胞生物学的验证；②阐明此通路对结肠癌侵袭转移的影响；③通过一系列体内外实验干预此信号通路，为结直肠癌侵袭转移诊疗提供潜在靶点。

Metastasis is the primary cause of poor prognosis of colon cancer. Our previous studies have demonstrate that : ① PP4C exhibited a higher expression in colon cancer, and contributed to metastasis and poor prognosis of colon cancer; ② Proteomic screening identified transcription factor Prox1 as a PP4C interaction partner, and formed PP4C/Prox1 complex; ③Gene expression profile studies demonstrated that PP4C and Prox1 could regulate the expression of IGF1R gene, thus leading to activation of the IGF1R signaling pathway and renders metastatic capacity to colon cancer. Based on these clues, we put forward the existence of the “PP4C/Prox1-IGF1R” signaling pathway, which participated in regulation of metastasis and contributed to poor prognosis of colon cancer. The present study aims to carry out the following research: ①Analysis of the regulatory role between PP4C,Prox1 with IGF1R, and elucidate the regulatory role through a series of biochemical and molecular biological assays; ② Verification of the contribution of “PP4C/Prox1-IGF1R” signaling pathway to colon cancer metastasis regulation; ③ Through a series of in vitro and in vivo assays to intervening the signaling pathway to provide potential predictive and treatment targets for the metastasis of colon cancer.