Dual role of fucosidase in cancers and its clinical potential
Jinxing Fu, Qing Guo, Yuan Feng, Peng Cheng, Anhua Wu
Abstract
Glycosidases and glycosyltransferases greatly impact malignant phenotype of tumors though genetics and epigenetics mechanisms. As the member of glycoside hydrolase (GH) families 29A, α-L-fucosidases (AFUs) are involved in the hydrolysis of terminal L-fucose residues linked via α-1,2, α-1,3, α-1,4 or α-1,6 to the reducing end of N-acetyl glucosamine (GlcNAc) of oligosaccharide chains. The defucosylation process mediated by AFUs contributes to the development of various diseases, such as chronic inflammatory diseases, immune disorders, and autoimmune diseases by reducing the interaction between fucosylated adhesion molecules supporting leukocyte extravasation. AFUs also impair crucial cell-extracellular matrix (ECM) interactions and presumably subsequent cell signaling pathways, which lead to changes in tumor function and behavior. There are two isoforms of AFUs in human, namely α-L-fucosidase 1 (FUCA1) and α-L-fucosidase 2 (FUCA2), respectively. FUCA1 is a p53 target gene and can hydrolyze different fucosylation sites on epidermal growth factor receptor (EGFR), thereby determining the activation of EGFR. FUCA2 mediates the adhesion between Helicobacter pylori and gastric mucosa and is upregulated in 24 tumor types. Besides, based on the participation of AFU in signaling pathways and tumor progression, we discuss the prospect of AFU as a therapeutic target.