雄激素非依赖性的产生是前列腺癌治疗的最大难题，深入研究雄激素非依赖性前列腺癌细胞的生物学特点及产生机制，对更好的实现精准医疗及新药的研发至关重要。我们前期研究发现：1）雄激素非依赖性前列腺癌细胞具有干细胞样特性及间质细胞的特性；2）Numb-/low代表一群雄激素非依赖性的前列腺癌细胞且在转移性前列腺癌组织中比例更高；3）与Numbhigh细胞相比，Numb-/low细胞富集间质细胞标记物（N-cadherin、Zeb1、Vimentin）的表达、且具有更强的迁移能力；4）上皮细胞标记物E-cadherin与Numb表达水平呈正相关。结合预实验结果，本项目拟研究Numb-/low细胞的上皮间质转化（EMT）特性并探索EMT是否富集Numb-/low细胞并增强其雄激素非依赖性的机制，通过寻找Numb与EMT相关基因的关键调控因子为雄激素非依赖性前列腺癌的诊疗提供新的线索及治疗靶点。

The emergence of castration-resistant prostate cancer (CRPC) is the biggest problem challenging current clinical treatments of prostate cancer. Deciphering the biological characteristics and molecular mechanism of the development of CRPC cells is critical for guiding precision medicine as well as developing new drugs. Our recent studies suggest that: 1) CRPC cells display the characteristics of stem-like cells and mesenchymal cells. 2) Numb-/low enriches an CRPC cell subpopulation and metastatic prostate cancer tissues have a higher proportion of Numb-/low cells. 3) Numb-/low cells have a higher expression of N-cadherin, Zeb1 and Vimentin and a stronger migration capability compared with Numbhigh cells. 4) There is a positive correlation between E-cadherin and Numb expression level. Thus, we tend to explore the Epithelial-Mesenchymal Transition (EMT) properties of Numb-/low prostate cancer cells and whether EMT enriches and enhances the androgen independence of Numb-/low cells. Moreover, we will track down key regulators between Numb and EMT-related genes to provide new insights into novel therapeutic strategies of CRPC.