肿瘤转移是癌症患者死亡的主要原因， Arf6小G蛋白持续活化促进癌细胞侵袭和迁移。我们实验室揭示了Arf6激活蛋白ACAP4参与趋化因子CCL18介导的乳腺癌转移。利用功能蛋白质组学筛选，我们最新鉴定了一种新的Arf6-ACAP4信号调节因子Acapin，预实验结果表明其能够抑制ACAP4的GAP活性并能被AKT磷酸化。我们拟依托本项目，综合利用生物化学、生物光谱学及生理学等实验技术方法，系统地研究和解析ACAP4如何介导线粒体动态性调控细胞迁移及肿瘤转移分子机制，从细胞器动力学及分子动态网络层面理解EGFR/PI3K/Arf6途径与EGFR/AKT途径在细胞迁移及肿瘤转移过程中的交互作用机理，为解析癌症转移与浸润的分子机制提供有效工具，并为临床干预靶点的确定提供理论依据。

Tumor metastasis is the leading cause of death in cancer patients. The continuous activation of Arf6 small G protein promotes cancer cell invasion and migration. Our laboratory revealed that the Arf6 activator protein ACAP4 is involved in the chemokine CCL18-mediated breast cancer metastasis.Using functional proteomics screening, we also identified a novel Arf6-ACAP4 signaling regulator, Acapin, which was shown to inhibit the GAP activity of ACAP4 and be phosphorylated by Akt. Based on this project, we aim to investigate how ACAP4 mediates cell migration and tumor metastasis through regulating mitochondria dynamic using multi-disciplinary techniques such as biochemistry, biospectroscopy and physiology. We expect to achieve a better understanding of the interaction mechanism between EGFR/PI3K/Arf6 pathway and EGFR/AKT pathway in cell migration and tumor metastasis from organelle dynamics and molecular dynamic networks. Our study will provide an effective tool for analysing the molecular mechanisms of cancer metastasis and infiltration, and provides a theoretical basis for the determination of clinical intervention targets.