PAK5是丝氨酸/苏氨酸激酶，在乳腺癌侵袭转移中的作用及其机制尚不清楚。本项目前期工作发现，PAK5能促进乳腺癌细胞EMT及乳腺癌干细胞标记物CD44表达。采用蛋白质谱分析技术，筛选出了PAK5新的互作蛋白-天冬酰胺氨肽酶DNPEP。已初步证实DNPEP能抑制乳腺癌细胞迁移，CD44表达及微球体形成。PAK5则磷酸化并负向调节DNPEP表达。本课题旨在进一步证实PAK5与DNPEP的相互作用并发现新的磷酸化位点；确定PAK5与DNPEP调控关系及机制；阐述DNPEP对乳腺癌细胞侵袭转移和乳腺癌干细胞样表型影响并寻找DNPEP调控CD44蛋白的机制；明确PAK5与DNPEP相互作用与临床乳腺癌病理分期，分子分型，病人生存和预后的关系。通过上述研究，使我们弄清PAK5介导的DNPEP磷酸化在乳腺癌转移及乳腺癌干细胞样表型中的作用及机制，为乳腺癌治疗提供分子靶标。

The role and mechanisms of PAK5 in invasion and metastasis of breast cancer are still unclear. Our previous study found that PAK5 could promote epithelial to mesenchymal transition and expression of breast cancer stem cell specific marker CD44. The aspartyl aminopeptidase(DNPEP) was identified a novel PAK5-interacting protein by Protein mass spectrometry technology. It was confirmed that DNPEP inhibited migration , CD44 expression and microsphere formation of breast cancer cells, while PAK5 phosphorylated DNPEP and negatively regulated its expression..In this project, We aim to confirm the interaction of PAK5 with DNPEP and find new phosphorylation site in DNPEP and to explore the mechanism for PAK5 modulating DNPEP expression. We plan to investigate the effects of DNPEP on invasion and metastasis and cancer stem cell-like phenotype of breast cancer and elucidate the new mechanisms for DNPEP regulating CD44 expression. We want know the correlation between the PAK5-DNPEP interaction and clinical pathological phase, molecular subtype, patients survival and prognosis. This project will make us understanding of the mechanistic role of PAK5-mediated DNPEP phophorylation in metastasis and cancer stem cell-like phenotype, providing a new molecular marker and therapeutic target for breast cancer treatment.