Expression and Impact of C1GalT1 in Cancer Development and Progression

SIMPLE SUMMARY: C1GalT1 is one of the enzymes that catalyze the addition of sugar residues to proteins (protein glycosylation). It specifically controls the synthesis and formation of a special disaccharide structure Galβ1,3GalNAcα-, which occurs predominately in cancer but rarely in normal cells. Recent studies have shown that C1GalT1 is overexpressed in many common cancers including colon, breast, gastric, lung, head and neck, pancreatic, esophageal, prostate, and hepatocellular cancer. C1GalT1 overexpression is also often associated with poorer prognosis and poorer patient survival. This review summarizes our current understanding of the expression of C1GalT1 in various cancers and discusses the impact of C1GalT change on cancer cell activities in cancer development and progression. ABSTRACT: C1GalT1 (T-synthase) is one of the key glycosyltransferases in the biosynthesis of O-linked mucin-type glycans of glycoproteins. It controls the formation of Core-1 disaccharide Galβ1,3GalNAcα- (Thomsen–Friedenreich oncofetal antigen, T or TF antigen) and Core-1-associated carbohydrate structures. Recent studies have shown that C1GalT1 is overexpressed in many cancers of epithelial origin including colon, breast, gastric, head and neck, pancreatic, esophageal, prostate, and hepatocellular cancer. Overexpression of C1GalT1 is often seen to also be associated with poorer prognosis and poorer patient survival. Change of C1GalT1 expression causes glycosylation changes of many cell membrane glycoproteins including mucin proteins, growth factor receptors, adhesion molecules, and death receptors. This leads to alteration of the interactions of these cell surface molecules with their binding ligands, resulting in changes of cancer cell activity and behaviors. This review summarizes our current understanding of the expression of C1GalT1 in various cancers and discusses the impact of C1GalT change on cancer cell activities in cancer development and progression.