结直肠癌是世界范围和我国高发的恶性肿瘤，肝转移是其致死的主要原因。课题组前期研究发现WTX能正向调节细胞骨架调控蛋白CAPZA1表达，且WTX通过抑制细胞骨架的重塑进而在抑制结直肠癌进展及肝转移中发挥重要作用。但CAPZA1在WTX调节细胞骨架稳定性过程中的具体作用及分子机制尚不完全清楚。预实验结合文献，我们推测WTX可能通过CAPZA1影响细胞骨架的解聚和重塑，稳定Cadherin–Catenin复合物的形成，调控细胞间黏附进而抑制结直肠癌肝转移。本研究拟利用细胞、原位裸鼠模型及WTX基因敲除小鼠模型，深入探讨WTX与CAPZA1/细胞骨架/CCC通路的相互作用关系及其在结直肠癌肝转移过程中的作用；筛选通路相关抑制剂，寻找抑制结直肠癌肝转移的新方法。该项目的完成，将进一步揭示WTX在抑制结直肠癌进展和肝转移过程中的分子机制，为抑制结直肠癌进展和肝转移挖掘新的治疗方向。

Colorectal cancer is a malignant tumor with a high incidence in the world and in China, and liver metastasis is the main cause of death. Our previous study found that WTX can positively regulated the expression of cytoskeleton regulatory protein CAPZA1 and WTX plays an important role in inhibiting the progression of colorectal cancer and liver metastasis by inhibiting the remodeling of cytoskeleton F-actin. However, the specific role and molecular mechanism of CAPZA1 in the regulation of cytoskeleton stability by WTX are not fully understood. Combined with pre-experimental verification, we predict that WTX may affect the remodeling of cytoskeleton and the formation of Cadherin-Catenin complex through CAPZA1, regulating the adhesion between cells and thus inhibits liver metastasis of colorectal cancer. In this study, we use cells, in situ nude mice and WTX knockout mice to explore the interaction between WTX and CAPZA1 / cytoskeleton / CCC pathway and its role in the process of liver metastasis of colorectal cancer; and to screen the pathway related inhibitors to find a new way to inhibit liver metastasis of colorectal cancer. This project will further improve the molecular mechanism of WTX in the process of inhibiting the progression of colorectal cancer and liver metastasis, and excavate new therapeutic targets for inhibiting the progression of colorectal cancer and liver metastasis.