CBX7调控胃癌干细胞特性及其机制研究

PcG members are associated with tumorigenesis and development of many tumors. In recent years, it is found that they play important roles in the ability of self-renewal of stem cells. Therefore, it is necessary to further study whether PcG family members are involved in cancer stem cell regulation and its mechanism. In our previous study, we isolated gastric cancer stem cell subpopulation through mammosphere culture and flow cytometry, and found that PcG family member CBX7 is highly expressed in gastric cancer stem cell subpopulation. Further studies show that CBX7 can regulate gastric cancer stem cell characteristics. We for the first time found that CBX7 regulated pAKT, pERK, and miR-21 expression in gastric cancer cells.The project intends to clarify the roles of CBX7 in regulating gastric cancer stem cells, including self-renewal, drug resistance, high metastasis and explore the possible mechanisms from traditional P16 protein, pAKT and pERK passway we have just found, miR-21 and its target gene. Completion of this project will help to further elucidate CBX7 protein function and the molecular mechanisms of gastric cancer stem cells regulation, providing the foundation and basis for specific protein target therapy of gastric cancer stem cells.

PcG家族成员与多种肿瘤的发生发展密切相关，近年的研究显示部分成员在干细胞的自我更新能力中发挥重要作用，因此有必要深入研究PcG家族成员调控肿瘤干细胞特性的作用及相关机制。我们前期通过微球体培养及流式细胞术，初步分离到胃癌干细胞亚群，发现其高表达PcG家族蛋白CBX7。进一步研究发现，CBX7可调控胃癌干细胞特性。同时，我们在胃癌细胞中新发现CBX7可调控pAKT、pERK蛋白及miR-21的表达。本项目拟阐明CBX7在调控胃癌干细胞三大特性（自我更新、对治疗的抵抗、高转移能力）中的作用，并从传统通路P16蛋白，我们新发现的pAKT通路，pERK通路，miR-21及其靶基因探索其调控机制。本项目的完成，将有助于进一步阐明CBX7蛋白的功能及其调控胃癌干细胞特性的分子机制，为以胃癌干细胞内特定蛋白为目标的靶向治疗提供基础与依据。