侵袭转移是导致结直肠癌预后差的重要因素。已知多种癌细胞可产生糖基化IgG（CIgG）并促进侵袭转移，但其机制尚不清楚。我们前期研究发现：结直肠癌CIgG高表达与患者不良预后显著相关；并可能通过E-cadherin调节细胞粘附连接及β-catenin/c-Myc通路促进肿瘤细胞侵袭迁移。本课题拟进一步明确CIgG在结直肠癌侵袭转移过程中的作用；明确CIgG可通过E-cadherin影响粘附连接结构调控结直肠癌细胞侵袭迁移；探索CIgG对E-cadherin/β-catenin复合体结合、β-catenin核质转运及c-Myc表达的影响；明确CIgG糖基化修饰在调控E-cadherin/β-catenin/c-Myc信号通路中作用及糖基化结构；在人结直肠癌类器官和裸鼠体内验证糖基化CIgG调控结直肠癌细胞侵袭迁移的机制。肿瘤特异性糖基化CIgG信号通路研究有望为结直肠癌诊治提供新靶点和新思路。

Invasion and metastasis are critical factors leading to worse prognosis of colorectal cancer patients. It has shown that glycosylated IgG can be expressed in several kinds of cancers and improves the invasion and metastasis, it is called cancer IgG(CIgG). Our preliminary work showed that high expression of CIgG was related to worse prognosis of colorectal cancer and CIgG might regulate the invasion and migration of colorectal cancer cells through E-cadherin interacting with adherent junction and β-catenin/c-Myc signaling pathway. In this study, we aim to illuminate the role of CIgG in regulating invasion and metastasis of colorectal cancer in further, to demonstrate CIgG could regulate invasion and migration through adherent junction mediated by E-cadherin, to explore the effect of CIgG on the interaction with complex of E-cadherin/β-catenin, nulceocytoplasmic transport of β-catenin and c-Myc expression, to clear the role of glycosylation of CIgG in regulating the pathway of E-cadherin/β-catenin/c-Myc and the structure of glycosylated fragment, and at last to verify the mechanism of tumor specific glycosylated CIgG regulating invasion and migration of colorectal cancer cells in organoids and animal experiment. The research of tumor specific glycosylated CIgG associated pathways might provide new candidate targets and therapeutic strategies for colorectal cancer.