FUT8 and Protein Core Fucosylation in Tumours: From Diagnosis to Treatment

Abstract

Glycosylation changes are key molecular events in tumorigenesis, progression and glycosyltransferases play a vital role in the this process. FUT8 belongs to the fucosyltransferase family and is the key enzyme involved in N-glycan core fucosylation. FUT8 and/or core fucosylated proteins are frequently upregulated in liver, lung, colorectal, pancreas, prostate,breast, oral cavity, oesophagus, and thyroid tumours, diffuse large B-cell lymphoma, ependymoma, medulloblastoma and glioblastoma multiforme and downregulated in gastric cancer. They can be used as markers of cancer diagnosis, occurrence, progression and prognosis. Core fucosylated EGFR, TGFBR, E-cadherin, PD1/PD-L1 and α3β1 integrin are potential targets for tumour therapy. In addition, IGg1 antibody defucosylation can improve antibody affinity, which is another aspect of FUT8 that could be applied to tumour therapy.

Inhibition of α(1,6)fucosyltransferase: Effects on Cell Proliferation, Migration, and Adhesion in an SW480/SW620 Syngeneic Colorectal Cancer Model

“…Core-α(1,6)fucose plays a relevant role in cell homeostasis, as revealed by its neonatal lethality in FUT8 -null mice [ 22 , 23 ], and the phenotypic complications of individuals harboring pathogenic variants of FUT8 [ 24 , 25 ]. Cancer is not an exception and, as a result, core fucosylation disorders have proven to be relevant in the pathogenesis and clinical outcome of cancer patients [ 26 , 27 ]. In this regard, our group reported increased α(1,6)FT activity and expression in the tumor tissue of CRC specimens [ 8 ], as well as their potential as a prognostic factor [ 9 ].…”

Identification of Novel Prognostic Markers Associated With Laryngeal Squamous Cell Carcinoma Using Comprehensive Analysis

“…Mutation of SLC35C1 was found to cause leukocyte adhesion deficiency, which was a rare congenital disease due to the defect in the biosynthesis of selectin ligands on leukocytes ( 48 ). Fucosylation has been found to be an important type of posttranslational modification in many types of cancer ( 49 ). Moriwaki et al.…”

CD44 Glycosylation as a Therapeutic Target in Oncology

“…All fucosylation reactions in cells are catalyzed by focusyltransferases (FUTs). To date, 13 FUTs—FUT1 to 11, protein O-focusyltransferase 1 (POFUT1) and POFUT—have been identified ( 80 ). After CD44 N-acetylglucosamine is modified by α-(1,3)-focusylation, it can further form a sialyl-Lewis X (sLeX) structure, which can effectively bind to E-selectin ( 81 , 82 ).…”

“…FUT8 has an important stabilizing effect on N-glycan structure, which allows FUT8 to regulate key glycoproteins. FUT8-mediated core fucosylation plays an important role in regulating the biological functions of EGFR, TGFBR, E-cadherin, PD1/PD-L1 and α3β1 integrin ( 80 ). However, there is still no report on the effect of removing core fucosylation modification from the CD44 protein.…”