乳腺癌发病率位列女性肿瘤首位，但其发生发展机制仍不太明确。我们前期研究发现，VASP在乳腺癌组织中的表达水平明显增高，与患者无病生存率呈负相关。并且VASP过表达促进乳腺癌细胞增殖和迁移，更为重要的是VASP和β-catenin蛋白表达水平在细胞核中明显增高，Wnt/β-catenin信号通路下游靶基因c-myc表达上调，并且VASP在细胞核中可能通过Dvl3与β-catenin/TCF4转录调控复合物结合，并增加其转录活性。通过过表达β-catenin和/或干扰VASP策略，结果显示β-catenin/TCF4转录调控复合物的转录激活功能的发挥需要VASP蛋白的辅助。因此，本项目拟阐释VASP作为β-catenin/TCF4转录调控复合物的共激活因子，增强Wnt/β-catenin信号通路靶基因的转录，从而促进乳腺癌细胞的增殖和迁移。项目将从信号通路角度，为研究乳腺癌发生发展提供新思路。

The incidence of breast cancer ranked first in female tumors, but the generation and development of breast cancer is still an unclear biological process. Our previous study revealed that higher VASP expression level in breast cancer tissue was correlated with lower disease free percent survival in breast cancer patients. In addition, overexpression of VASP could promote the proliferation and migration of breast cancer cells, significantly elevate the protein expression level of VASP and β-catenin in nucleus, and upregulate the expression level of c-myc, which is a typical target gene of Wnt/β-catenin signaling pathway. Moreover, VASP could bind to the β-catenin/TCF4 transcription-regulation complex via Dvl3 in the nucleus and increase the activity of β-catenin/TCF4 transcription-regulation complex. By overexpressing β-catenin and/or knocking down VASP inside cells, it is shown that the transcriptional activation function of the β-catenin/TCF4 transcription-regulation complex requires assistance of VASP protein. Therefore, this project intends to investigate the role of VASP in activating the transcription of the target genes in Wnt/β-catenin signaling pathway as a coactivator of transcription-regulation complex during promotion the proliferation and migration of breast cancer cells, which will be benefit for better understanding a novel signaling pathway in breast cancer development.