Previous studies have shown that the main function of VASP is to regulate the cytoskeleton and play an important role in promoting tumor cell metastasis. In this study, we first reveal that VASP is located in the nucleus of breast cancer cells and elucidate a Wnt/β-catenin/VASP positive feedback loop. We identify that VASP is a target gene of Wnt/β-catenin signaling pathway, and activation of Wnt/β-catenin signaling pathway can significantly upregulate VASP protein expression, while upregulated VASP protein can in turn promote translocation of β-catenin and DVL3 proteins into the nucleus. In the nucleus, VASP, DVL3, β-catenin, and TCF4 can form VASP/DVL3/β-catenin/TCF4 protein complex, activating Wnt/β-catenin signaling pathway, and promoting the expression of target genes VASP, c-myc, and cyclin D1. Thus, our study reveals that there is a Wnt/β-catenin/VASP malignant positive feedback loop in breast cancer, which promotes the proliferation and migration of breast cancer cells, and breaking this positive feedback loop may provide new strategy for breast cancer treatment.

先前的研究表明，VASP的主要功能是调节细胞骨架，并在促进肿瘤细胞转移中起重要作用。在这项研究中，我们首先揭示了VASP位于乳腺癌细胞核中，并阐明了Wnt /β-catenin/ VASP阳性反馈环。我们确定VASP是Wnt /β-catenin信号通路的靶基因，激活Wnt /β-catenin信号通路可以显着上调VASP蛋白的表达，而上调的VASP蛋白又可以促进β-catenin和DVL3蛋白的转运进入细胞核。在细胞核中，VASP，DVL3，β-catenin和TCF4可以形成VASP / DVL3 /β-catenin/ TCF4蛋白复合物，激活Wnt /β-catenin信号通路，并促进靶基因VASP，c-myc，和细胞周期蛋白D1。因此，