The metastatic potential of malignant tumor has been shown to be correlated with the increased expression of tri- and tetra-antennary beta 1,6-N-acetylglucosamine (beta 1,6-GlcNAc) N-glycans. In this study, We found that GnT-V expression was negatively correlated with receptor protein tyrosine phosphatase type mu(RPTP mu) in human glioma tissues. To study whether RPTP mu is a novel substance of GnT-V which further affect RPTP mu's downstream dephosphorylation function, we preform lentiviral infection with GnT-V gene to construct stably transfected GnT-V glial cell lines. We found RPTP mu undergone severer cleavage in GnT-V transfected glioma cells compare to Mock cells. RPTP mu intracellular domain fragments increased while beta 1,6-GlcNAc-branched N-glycans increased, in consistent with the decrease of RPTP mu's catalytic activity. The results showed that abnormal glycosylation could decrease the phosphorylation activity of PTP mu, and affect PLC gamma-PKC pathways. Both protease inhibitor Furin and N-glycan biosynthesis inhibitor swainsonine could decrease cell mobility in GnT-V-U87 transfectants and other glioma cell lines. All results above suggest increased post-translational modification of RPTP mu N-glycans by GnT-V attenuates its tyrosine phosphatase activity and promotes glioma cell migration through PLC gamma-PKC pathways, and that the beta 1,6-GlcNAc-branched N-glycans of RPTP mu play a crucial role in glioma invasivity. (C) 2018 Elsevier Inc. All rights reserved.