Fig. 2

Function of glycosylation in gliomas. Glycosylation impacts on glioma progression include regulating protein function (a), affecting cell‒cell or cell‒matrix interactions (b), and triggering downstream pathways (c), which ultimately produce malignant progression of gliomas (d), and various types of research have gradually advanced. (b) For changes in cell‒cell or cell‒matrix interactions, studies of glioma cell‒ECM interactions have found that gliomas can interact with the ECM through cell surface proteins, including chondroitin sulfate proteoglycans (CSPG) of the lectican family, GPR56, β1 integrins, etc. In addition, N402 glycosylation deficiency disrupts N-cadherin stabilization, ultimately inhibiting cadherin-mediated cell‒cell adhesion and promoting cell migration. PTPµ can be differentially glycosylated, full-length PTPµ produces a larger shed extracellular fragment PTPµ after direct cleavage by ADAM protease, a process that impacts cell‒cell interactions. (c) More specifically, the effect of glycosylation on the malignant progression of glioma can be achieved by triggering downstream pathways. For instance, FUT8 can be involved in altering the fucosylation status of MET and EGFR, and its knockdown or overexpression corresponds to the decrease and increase in the binding of LCA to MET and EGFR in glioma cells, and further, the HGF/MET signaling pathway is significantly activated by it. Whereas down-regulation of GALNT2 expression inhibited O-glycosylation, phosphorylation, and its downstream PI3K/Akt/mTOR pathway of EGFR, overexpression of GALNT2 had the opposite effect. In addition, ectopic expression of the highly glycosylated protein MUC4 regulates EGFR expression. Among other pathways, the ability of GPR56 to activate the β-catenin/TCF pathway may be involved in the transition from benign tumors to invasive metastatic cancers. Downregulation of Hsc70 may influencethe glycosylation and maturation of substrate integrin β1 by regulating the protein folding of β4GalT5, reduce the expression levels of β4GalT5 downstream signaling proteins p-ERK1, p-JNK1 and p-AKT. (d) The effects above can ultimately promote the proliferation, invasion and migration of glioma cells