FUT7 promotes the malignant transformation of follicular thyroid carcinoma through α1,3-Fucosylation of EGF receptor.

Abstract Aberrant protein glycosylation is involved in many diseases including cancer. This study investigated the role of fucosyltransferase VII (FUT7) in the progression of follicular thyroid carcinoma (FTC). FUT7 expression was found to be upregulated in FTC compared to paracancerous thyroid tissue, and in FTC with T2 stage of TMN classification compared to FTC with T1 stage. FUT7 overexpression promoted cell proliferation, epithelial–mesenchymal transition (EMT), and the migration and invasion of primary FTC cell line FTC-133. Consistently, FUT7 knock-down inhibited cell proliferation, EMT, as well as the migration and invasion of the metastatic FTC cell line FTC-238. Mechanistic investigation revealed that FUT7 catalyzed the α1,3-fucosylation of epidermal growth factor receptor (EGFR) in FTC cells. The extent of glycan α1,3-fucosylation on EGFR was positively correlated with the activation of EGFR in the presence/absence of epidermal growth factor (EGF) treatment. Furthermore, FUT7 was shown to enhance EGF-induced progression of FTC cells through mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways. These findings provide a new perspective on FUT7 that may be a novel diagnostic and therapeutic target of FTC.