癌细胞转移是癌症患者死亡的主要原因, 深入阐明其机制具有重要理论与实践意义。小G蛋白Rap1特异性GAP（SPA-1）是乳腺癌转移效率修饰位点Mtes1中主要候选基因之一。我们前期研究发现：乳腺癌转移患者癌细胞SPA-1表达显著高于非转移患者，而SPA-1表达沉默的人乳腺癌细胞迁移能力明显下降；SPA-1可与integrin相互作用；可促进MMP9表达；诱导VEGF表达促进肿瘤血管新生。上述实验进展提示，SPA-1是参与癌细胞转移的关键分子。本项目拟采用细胞力学、双光子显微成像和高分辨光声成像等技术在细胞和整体动物水平阐述SPA-1与integrrin直接相互作用调控肿瘤细胞骨架重塑；揭示通过影响FAK磷酸化等信号通路促进蛋白酶表达与活性而促进肿瘤组织胞外基质降解以及诱导VEGF表达而促进肿瘤组织血管新生的精细分子机制，为基于SPA-1的癌症转移早期诊断和干预策略提供实验依据。

Cancer metastasis is the main cause for the dearth of cancer patients. To unravel the mechanism of cancer metastasis is now becoming the focus of current cancer researches. SPA-1 (signal induced proliferation -associated protein-1) is a Rap1GAP which plays an important role in cell proliferation, adhesion, and migration. During a survey of breast cancer patients, we found SPA-1 protein is overexpressed in high grade breast tissues and migrated cancer cells both in breast tissue and lymph nodes. SPA-1 also promotes MDA-MB-231 cell invation and migration in vitro. These findings suggest that SPA-1 protein is probably a novel target molecule of cancer metastasis.This project aims to dissect the mechanism by which SPA-1 promotes breast cancer metastasis at multiple levels in the following studies: 1) Confirm that SPA-1 promotes breast cancer cell metastasis both in vitro and in vivo. 2) Dissect the mechanisms that how SPA-1regulates breast cancer cell morphological changes and signal transduction pathways to accelerate its invasion and migration; 3) Investigate the interaction between SPA-1 and integrins; 4) Investigate the interaction of SPA-1 regulated breast cancer cell with endothelial cells to understand how cancer cells set up a benefit environment to metastasis. Our ultimate goals are to create a novel biomarker for early detection of cancer metastasis and to develop effective therapeutic target for cancer treatment.