癌细胞逃逸是癌症转移导致患者死亡的主要原因之一。信号诱导增殖相关蛋白SIPA1能促进乳腺癌细胞侵袭转移，且氧化还原状态的调控在乳腺癌细胞转移进程中起重要作用。本项目拟检测乳腺癌细胞Redox值和SIPA1表达水平，明晰氧化还原状态和SIPA1表达水平与乳腺癌转移程度的相关性；检测乳腺癌细胞中线粒体功能特征以及ATP量，结合Chip测序分析候选基因，确定SIPA1直接调控乳腺癌细胞氧化还原状态的关键分子及信号通路；进一步用乳腺癌细胞外泌体处理肿瘤微环境相关的血管内皮细胞和巨噬细胞，检测细胞氧化还原状态、血管内皮细胞通透性和巨噬细胞转型，明晰SIPA1通过调控乳腺癌细胞基因表达、改变癌细胞外泌体组分、调节氧化还原状态的关键分子和信号通路，揭示SIPA1调控乳腺癌细胞逃逸、透过血管内皮细胞实现转移的调控机制。本项目将发现调控乳腺癌细胞转移新靶点，为转移性乳腺癌检测和治疗提供技术支撑和理论依据。

Cancer cells escape is the main cause of death in patients with tumor metastasis. As one of the primary candidate underlying the metastasis efficiency modifier locus 1, SIPA-1 has been found to be capable of promoting breast cancer cell invasion and metastasis. It is well known that regulation of cellular redox status plays important role during breast cancer metastasis. In this project, we are going to detect the cellular redox status and SIPA1 expression in breast cancer cells, to clarify the correlation of cellular redox status and SIPA1 expression level with the metastatic status of breast cancer. We will also study the functional feather and ATP production in mitochondria of breast cancer cells, incorporating the candidate genes selected from chip-seq data, to identify the key molecules and signaling pathways to participate the regulation on redox status of breast cancer cell by SIPA1. Moreover, we are going to treat vascular endothelial cells and macrophage cells with exosomes secreted from breast cancer cells, to clarify the molecules and pathways that play crucial roles during the process that SIPA1 promotes certain genes expression in breast cancer cells, to affect the composition of exosomes from breast cancer cells and regulate the cellular redox status. Finally, we will discover the molecular mechanism of SIPA1 on regulating the breast cancer cell escape process and invasion into vascular endothelial cells to approach metastasis. Furthermore, we are going to discover the new targets to regulate the breast cancer metastasis, and to provide theoretical and technic supporting for breast cancer diagnose and therapy development.