针对肿瘤干细胞的研究为治疗胃癌提供了新思路，但目前缺乏有效靶点。RNF43是新近测序发现的在胃癌中突变较高的基因，我们率先证实了它的抑癌作用及其作为预后标志物的转化价值，进一步研究发现，RNF43能调控胃癌干细胞的成球能力并与Wnt/β-catenin活性负相关。结合文献报道，本项目将在前期基础上围绕胃癌干细胞和RNF43开展如下研究：①用原位杂交等技术从组织和细胞水平探究RNF43、胃癌干细胞及Wnt通路关联；②体外成球、裸鼠成瘤和microPET/CT等实验技术体内体外阐明RNF43对胃癌干细胞的自我更新、侵袭等恶性特性的调控及其对Wnt通路影响；③借助iTRAQ蛋白质组学等技术揭示RNF43通过Wnt通路影响胃癌干细胞恶性特性的调控机制。本项目将有助于明确RNF43作为胃癌干细胞靶点的转化价值，丰富基于异常Wnt通路的调控网络在胃癌干细胞特性维持中的理论认知，为相关药物开发提供借鉴。

Targeting cancer stem cells provides new strategy to eliminate gastric cancer, but no feasible target is available. RNF43 are recently found by sequence analysis and mutates highly in gastric cancer. We have reported its tumor-suppress role and prognostic potential. An in-depth investigation has reveals its impact on tumorsphere of gastric cancer stem cell and negative association with Wnt/β-catenin signal activity. Based on previous reports and investigation, the aims of present study are as follows: to investigate the association among RNF43, gastric cancer stem cell and Wnt signal by in situ hybridization at tissular and cellular level; to investigate the impact of RNF43 on biological behavior of gastric cancer stem cell and Wnt signal pathway in vivo and in vitro; to elucidate the molecular mechanism that how RNF43 regulates biological behavior via Wnt signal pathway by iTRAQ analysis. The study would contribute to illuminating the translational value of RNF43 as the target of gastric cancer stem cell, enriching our knowledge about the role of Wnt signal pathway on maintaining biological behavior of gastric cancer stem cell and providing valuable information for drug development.