Alteration of extracellular glycosylation is a hallmark of malignant characteristics. In this study, we revealed that
fucosyltransferase 8 (FUT8), an
enzyme that mediates the core fucosylation of N-linked glycosylation, is an important regulator of malignant characteristics in human
glioma that acts by modifying the activities of both the
HGF receptor (MET) and
epidermal growth factor receptor (EGFR).
mRNA and
protein expression levels of FUT8 were frequently upregulated in
gliomas, and these events were showed positive correlations with advanced
tumor grade, recurrence, and decreased overall survival. Silencing FUT8 expression in
glioma cells suppressed cell growth, migration, and invasion, whereas overexpression of FUT8 was sufficient to enhance these phenotypes. Mechanistic investigations revealed that FUT8 was involved in the alteration of fucosylation status that was attached to MET and EGFR, changing MET responses after HGF stimulation, as well as in the transactivation of EGFR. Importantly, altering FUT8 expression or using the fucosylation inhibitor 2F-peracetyl-fucose sensitized the efficacy of of
temozolomide (TMZ)
therapy. Collectively, these results suggested that FUT8 dysregulation contributed to the malignant behaviors of
glioma cells and provide novel insights into the significance of fucosylation in
receptor tyrosine kinase activity and TMZ resistance.