GnT-IVa通过调控β-1,4 N-糖结构介导EMT影响细胞迁移的机制研究

上皮间质细胞转化（EMT）在发育和肿瘤发生等病理生理过程中发挥重要作用。GnT-IVa是N乙酰氨基葡萄糖转移酶家族成员，特异性调控N糖核心上β-1,4分支的形成，但功能不清。课题组发现当GnT-IVa表达改变时可导致细胞形态、EMT分子Marker、intergrin蛋白糖链以及运动迁移能力的改变。为此，本研究提出“GnT-IVa→细胞表面N糖基化异常→粘附因子功能变化→EMT→细胞迁移”假设，并将构建GnT-IVa不同表达水平的细胞株，研究GnT-IVa、N糖链与E-cadherin和intergrin等细胞粘附因子的关系，分析GnT-IVa调控的β-1,4 N糖链在EMT中的作用，进而阐明糖链结构影响EMT调控细胞迁移的机制。此研究对揭示GnT-IVa通过调控粘附因子糖链结构影响EMT基本生物学过程，进而调控细胞迁移具有重要的理论价值，也将为靶向药物受体以及抗肿瘤转移研究提供新的思路。

Epithelial mesenchymal transition (EMT) plays an important role in the development and tumorigenesis process. GnT-IVa is one of the N-acetylglucosaminyltransferase, which could catalyze the formation of the GlcNAC β1-4 branch. And the function of GnT-IVa is unclear. Our previous results showed that the change of the expression of GnT-IVa could induce the variety of the cell morphology, marker of EMT and migration. A hypothesis was suggested that the GnT-IVa→abnormal N-glycosylation→functional change of adhesion factor→EMT→cell migration. We are planing to construct the recombinant of different expression level of GnT-IVa to clearify the relation among the GnT-IVa, β-1,4 N-gkycan, EMT and migration. Furthermore, the related pathway will be analyzed to elucidate the correlations of GnT-IVa with cell migration. The results will helpful to academic value on the in-depth analysis of the mechanism of the cell biology function of the glycan and glucosaminyltransferase. And this study will be provide a new research method on the protein post-translational modification basic data for exploring.