乳腺癌是造成女性癌症死亡的首位因素，发病机制不清。申请人前期研究发现WARS2在乳腺癌组织有表达，且表达量与病人预后呈显著负相关。前期体外实验显示过表达WARS2可有效促进乳腺癌细胞增殖和侵袭，并伴有互作蛋白APP的上调和GSK3β的磷酸化增加。WARS2在乳腺癌中的作用尚未见报道。综合以上研究基础并结合CHIP-Seq数据、TCGA公共数据库及表达谱数据，科学假设：WARS2可能与APP蛋白相互作用后促进GSK3β磷酸化，导致β-catenin降解受阻而入核转录增加，从而发挥促进乳腺癌增殖、侵袭的功能。本项目拟利用基因敲除、细胞迁移、裸鼠成瘤模型等手段，从“细胞-动物-临床”多层次深入研究WARS2调控乳腺癌增殖与侵袭的机制，为乳腺癌靶向治疗和预后判断提供新的参考，具有重要的临床意义。

Breast cancer is the first cause of female cancer death, and the pathogenesis is unclear. Earlier studies showed that WARS2 was highly expressed in breast cancer tissues, which was negatively correlated with the prognosis of patients. Early in vitro experiments showed that knockdown of WARS2 could effectively inhibit the proliferation and invasion of breast cancer cells, accompanied by down-regulation of APP and phosphorylation of GSK3β, which indicate WARS2 may promote breast cancer by activating APP/GSK3β signal pathway, but not yet confirmed. Based on the above study and combined with CHIP-Seq data, TCGA public database , we speculate that WARS2 may play a role in promoting the proliferation and invasion of breast cancer. The aim of this project is to explore the mechanism of WARS2 regulation of breast cancer proliferation and invasion from molecular, cellular and whole level by gene knockdown, cell migration and nude mouse t model. We hope it is going to provide new insights into therapeutic therapy of breast cancer, which has important clinical significance.