中文摘要
胃肠道黏液细胞分泌的可溶性小分子多肽三叶因子1即TFF1在黏膜损伤、炎症保护及肿瘤发展中均具有重要作用,不仅是潜在的新型肿瘤标志物,而且还是胃癌抑癌基因。本课题前期研究发现,TFF1与钙离子通道Piezo1具有强结合能力,通过Piezo1介导TFF1可以促进胞内钙离子浓度上调,并抑制细胞跨膜侵袭。本项目拟进一步系统阐明:1)Piezo1 与TFF1以配体-受体形式相互结合;2)TFF1通过其受体Piezo1蛋白介导调控胞内Ca2+浓度的作用与机制;3. TFF1在Piezo1蛋白介导下依赖于Calpain-Talin-Integrin途径调控胃癌细胞转移侵袭的作用与机制。综上,本课题明确TFF1以配体-受体作用模式通过其受体Piezo1蛋白介导参与胃癌发生发展调控,树立TFF1为胃癌早诊早治新靶点,具有很好的创新性与临床应用价值。
英文摘要
Soluble small molecule polypeptide trefoil factor 1 (TFF1) plays an important role in mucosal injury, inflammation and tumor development. TFF1 is not only a potential new tumor markers, but also a tumor suppressor genes in gastric cancer. In this study, we found that TFF1 and calcium channel Piezo1 have strong binding ability. TFF1 can promote the up regulation of intracellular calcium concentration, and inhibit the invasion of cell membrane via Piezo1 mediated. This project aims to further clarify the system: 1) Piezo1 is ligand receptor for TFF1 with strong binding ability; 2) effects and mechanism of TFF1 in mediating Ca2+ concentration and cell invasion via a manner that mediated by its receptor Piezo1; 3) TFF1 and Piezo1 protein mediate gastric cancer cell invasion by Calpain-Talin-Integrin dependent pathway. In summary, this topic make it clear that TFF1 play a gastric cancer inhibitory effect mediated by its ligand receptor Piezo1 protein. And we establish TFF1 as a new target for early diagnosis and early treatment of gastric. Our study has good innovation and clinical application value.
