糖基转移酶超家族在肿瘤转移中的作用

The Role of Glycosyltransferase Superfamily in Tumor Metastasis

蛋白质的糖基化修饰主要包括N-连接糖基化、O-连接糖基化和糖基磷脂酰肌醇锚定连接.与核酸和蛋白质不同,糖链的合成过程并不遵循传统的基因信息传递的中心法则,主要由一系列催化糖苷键形成的糖基转移酶完成.异常糖基化修饰被认为与恶性肿瘤的发生发展和临床预后密切相关.研究表明,糖基转移酶的表达及其糖链结构的异常可通过调节肿瘤细胞与细胞外基质的相互作用,继而影响肿瘤转移的关键步骤,如上皮间质转化(E-钙黏着蛋白、N-钙黏着蛋白)、细胞的移动性(整合素β1和α5)、侵袭(基质金属蛋白酶MMPs)、浸润(唾液酸化Lewis抗原sLeX和sLeA).本文主要就唾液酰基转移酶、岩藻糖基转移酶和N-乙酰氨基葡萄糖转移酶等三大糖基转移酶家族的结构和生物学功能及其在肿瘤转移中的作用作一综述,以期为肿瘤转移的预测和诊断提供新思路.

Protein glycosylation modification includes N-linked glycosylation, O-linked glycosylation and glycosylphosphatidylinositol anchor glycosylation. Difference from nucleic acids and proteins, the synthetic process of glycans is mainly completed by a series of glycosyltransferases which catalyze glucosidic bond, not followed the traditional central dogma of genetic information transmission. Abnormal glycosylation modification is considered to be closely related to the occurrence, development and clinical prognosis of malignant tumor.Previous studies have shown that the abnormity of glycosyltransferases expression and glycans structure affects key steps of the metastatic cascade, such as epithelial-mesenchymal-transition（E-cadherin, N-cadherin）, cell motility（integrin β1 and α5）, invasion（matrix-metalloproteinases）, extravasation（s Lex and s Lea）, which by regulating the interaction between tumor cells and extracellular matrix. In this review, we mainly focus on the structures and biological functions of three glycosyltransferase families（sialyltransferases, fucosyltransferases and N-acetylglucosaminyltransferases）, and their roles in tumor metastasis, hoping it can provide new ideas for the prognosis and diagnosis in tumor metastasis.