乳腺癌是女性肿瘤研究的热点领域之一，其最常见的转移方式为淋巴结转移。目前，上皮间质转化（EMT）是乳腺癌转移的公认学说，但并不能阐述其淋巴转移的“偏好”。我们的前期研究通过对国际通用临床数据库（TCGA和GEO）的大量数据分析和对患者肿瘤标本的检测，在分子基础上初步观察到PROX1分子可能特异性调控其下游β-catenin/（ZEB1、ZEB2）通路并维系乳腺癌细胞间质化特性。在此基础上，我们大胆提出“横跨淋巴管发育和癌症两大领域的PROX1基因的表达，是决定乳腺癌的EMT及其特异性淋巴转移的驱动因素”。本项目将以不同表达PROX1的细胞模型、SCID鼠原位瘤模型、临床组织标本为研究对象，分析PROX1调控β-catenin/（ZEB1、ZEB2）信号变化对乳腺癌上皮间质转化、淋巴转移及化疗耐药的影响，阐明对乳腺癌恶性进展调控的新机制。

The mechanism of breast cancer (BRCa) is one of the hottest areas of cancer research in females, and the most common way for BRCa metastasis is via lymph nodes. Currently, epithelial mesenchymal transition (EMT) is the main theory for BRCa metastasis, but it still has limitations to illustrate why BRCa has preference to metastasis by lymph nodes. By analyzing international standard database（TCGA and GEO）, our clinic samples and molecular results, our study has successfully confirmed that PROX1 can specifically regulate the β-catenin/（ZEB1、ZEB2） and maintain mesenchymal properties. Therefore, we propose a hypothesis that "The expression of PROX1, a protein which involved in both lymphatic and cancer development, determines the EMT of BRCa and specificity of lymph nodes metastases as an upstream driver". This project will analyze roles of PROX1 in the regulation of β-catenin/（ZEB1、ZEB2） signaling during the EMT, lymphatic metastasis and chemoresistance in BRCa based on different PROX1-expressing cell models, the orthotopic animal models and clinical tissue samples. The study will clarify the novel mechanism contributing to the malignant progression of BRCa .