Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer  

作　　者：Jing Zhang Peter ten Dijke Manfred Wuhrer Tao Zhang 

机构地区：[1]Oncode Institute and Cell Chemical Biology,Leiden University Medical Center,2300 RC Leiden,The Netherlands [2]Center for Proteomics and Metabolomics,Leiden University Medical Center,Leiden,The Netherlands

出　　处：《Protein & Cell》2021年第2期89-106,共18页蛋白质与细胞（英文版）

摘　　要：Glycosylation is a common posttranslational modification on membrane-associated and secreted proteins that is of pivotal importance for regulating cell functions.Aberrant glycosylation can lead to uncontrolled cell proliferation,cell-matrix interactions,migration and differentiation,and has been shown to be involved in cancer and other diseases.The epithelial-to-mesenchymal transition is a key step in the metastatic process by which cancer cells gain the ability to invade tissues and extravasate into the bloodstream.This cellular transformation process,which is associated by morphological change,loss of epithelial traits and gain of mesenchymal markers,is triggered by the secreted cytokine transforming growth factor-β(TGF-β).TGF-βbioactivity is carefully regulated,and its effects on cells are mediated by its receptors on the cell surface.In this review,we first provide a brief overview of major types of glycans,namely,N-glycans,O-glycans,glycosphingolipids and glycosaminoglycans that are involved in cancer progression.Thereafter,we summarize studies on how the glycosylation of TGF-βsignaling components regulates TGF-βsecretion,bioavailability and TGF-βreceptor function.Then,we review glycosylation changes associated with TGF-β-induced epithelial-to-mesenchymal transition in cancer.Identifying and understanding the mechanisms by which glycosylation affects TGF-βsignaling and downstream biological responses will facilitate the identification of glycans as biomarkers and enable novel therapeutic approaches.

关 键 词：CANCER epithelial-to-mesenchymal transition GLYCOSPHINGOLIPIDS N-GLYCOSYLATION Oglycosylation transforming growth factor-β 

分 类 号：R730[医药卫生—肿瘤]