DAX1和EZH2在宫颈癌干细胞中相互作用的机制研究

Cancer stem cells (CSCs) are crucial in the initiation, development and progression of various human carcinomas，and also important in cancer metastasis, reoccurance, and drug resistance. Our previous studies showed that human cervical cancer stem cells had been firstly isolated and identified; and found that transcriptative suppressors,both DAX1 and EZH2 which might enhance the protein expression for each other, could promote the cervical carcinogenesis and development, respectively. In the present project, we plan to study: (1) DAX1 functions and molecular mechanism in cervcal cancer stem cells, (2) EZH2 functions and molecular mechanism in cervcal cancer stem cells, (3) Molecular mechanism of interaction between DAX1 and EZH2 in cervical cancer and human embryonic stem cells,(4) Molecular mechanism of interaction between DAX1 and EZH2 in cervical cancer stem cells. Through all above studies, we attempt to clarify the role by which DAX1 and EZH2 cooperate to function in cervical cancer stem cells. Results from such studies will provide new inofmration from the area of transcription repressors, such as DAX1 and EZH2, to develop novel stratigies to intervene cervical cancer targeting cervical cancer stem cells.

肿瘤干细胞是癌症发生、发展的主要动因,也是癌症治疗三大难点--复发,转移及抗药性产生的主要载体。 我们的前期研究已经在国内外率先分离鉴定出宫颈癌干细胞; 证实转录抑制因子DAX1和EZH2能够促进宫颈癌细胞的增殖和肿瘤形成; 并发现DAX1和EZH2能够交互促进彼此蛋白的表达。本项目拟研究：(1)DAX1对宫颈癌干细胞功能的影响及分子机制；（2）EZH2对宫颈癌干细胞功能的影响及分子机制；（3）DAX1和EZH2在宫颈癌及胚胎干细胞中相互作用的分子机制；（4）DAX1和EZH2的相互作用对宫颈癌干细胞功能的影响及分子机制。通过上述研究，我们拟阐明DAX1和EZH2在宫颈癌干细胞中相互作用的分子机制，为靶向宫颈癌干细胞从转录抑制因子方面探寻新靶点。

肿瘤干细胞既是癌症发生发展的主要动因，又是癌症治疗三大难点-复发、转移和耐药性产生的关键载体。本项目前期已经在国内外率先分离鉴定出宫颈癌干细胞; 证实转录抑制因子DAX1和EZH2能够促进宫颈癌细胞的增殖和肿瘤形成; 并发现DAX1和EZH2能够交互促进彼此蛋白的表达。在本项目的支助下，我们发DAX1和EZH2均可促进宫颈癌干细胞的干性特征，包括体内外自我更新能力，成瘤能力，分化能力及抗化疗药物等特性。机制研究发现二者均一致性的通过激活Wnt信号转导通路从而发挥作用；进一步的蛋白组学结合蛋白-蛋白相互作用技术进一步分析二者的相互作用及调节关系。本课题通过研究干细胞相关基因DAX1和EZH2的相互作用机制和调控激活Wnt信号转导通路调节宫颈癌干细胞特性，为靶向宫颈癌干细胞新治疗技术的开发提供理论基础