N-糖基化修饰对CD82调控人结肠癌转移机制的研究

四跨膜蛋白CD82是广谱的肿瘤转移抑制因子，当其发挥抑制肿瘤转移的功能时，N-糖基化修饰是具有重要意义的翻译后修饰，去除N-糖链后CD82即失去转移抑制作用，但N-糖链调控CD82抗转移的作用机制尚不清楚。已知CD82抑制转移的主要途经是在细胞膜表面形成功能性复合体，进而影响与粘附分子的相互作用，膜受体的活化，并下调与细胞运动及迁移调控相关的信号途经。本研究以淋巴结高转移而CD82无表达的结肠癌细胞株SW620为细胞模型，构建不同N-糖基化位点突变的CD82突变体，揭示N-糖基化修饰介导CD82在膜微区功能性复合体的形成及定位，以及不同N-糖基化修饰对表皮生长因子受体磷酸化及其下游细胞内与转移相关的信号转导通路的影响，阐明不同N-糖基化修饰在CD82抗结肠癌肿瘤细胞转移中的作用机制。

Tetraspanin CD82 is a wide-spectrum suppressor for cancer invasion and metastasis. The N-glycosylation of CD82 is necessary for its inhibitory effect on cancer. Deletion of N-linked oligosaccharide chain, CD82 would abolish the effect of CD82-suppressed cell motility and migration, however the mechanism remains unclear. It is known that CD82 suppresses cancer metastasis mainly through influencing function of some membrane proteins such as adhesion molecules and growth factor receptors, leading to down-regulation of intracellular signaling pathways which control the cell metastasis. In this study, we use SW620 cell, a colon cancer cell line with high lymph node metastatic potential but no expression of CD82, to clarify the effect of diverse N-Glycosylation of CD82 modification on the formation of membrane functional complex, phosphorylation of EGFR and the activity of EGFR signaling. This research would be helpful to elucidate the molecular mechanism by which site of N-Glycosylation affects CD82 inhibiting the motility and migration of SW620 cell.