Abstract

Fucosyltransferase 8 (FUT8), a glycosyltransferase responsible for core fucosylation, is overexpressed in numerous cancers and promotes many malignant processes such as cell proliferation, invasion and migration. Transforming growth factor-β (TGF-β) stimulation promotes epithelial–mesenchymal transition (EMT), a pivotal process indicating the invasion and metastasis of glioblastoma (GBM). However, the mechanism underlying the impact of FUT8 on the TGF-β signalling pathway in GBM progression remains largely unexplored. Our data revealed that FUT8 was highly expressed in patients with GBM and was associated with poor outcomes. FUT8 knockdown inhibited TGF-β-induced EMT, whereas FUT8 overexpression promoted TGF-β-induced EMT in vitro and in vivo. Mechanistic investigations revealed that FUT8 expression increased during TGF-β stimulation. In addition, the core fucosylation of TGF-β receptor complexes decreased after FUT8 knockdown. Moreover, the expression of E2F4, a transcription factor upregulated upon TGF-β stimulation, was shown to directly regulate the expression of FUT8 via a TGF-β-induced non-Smad signalling pathway. Our results elucidated a new mechanism facilitated by E2F4-FUT8-mediated receptor core fucosylation that promotes TGF-β signalling and EMT, ultimately driving the invasion and metastasis of GBM cells.