Expression and Impact of C1GalT1 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.

Advances in the Immunomodulatory Properties of Glycoantigens in Cancer

“…Indeed, increased activity or expression of sialyltransferases leads to the hypersialylation of cell surfaces, which as stated before is one of the most common glycosylation changes that occurs in tumours [48]. Furthermore, an upregulation of the TF antigen (Gal1,3-GalNAc 1-O-Ser/Thr) can be the consequence of upregulation of T-synthase [83]. Interestingly, it would seem that hormone therapy of breast cancer cells and oxidative stress induced the expression of incomplete TACAs in O-glycans [84] through a process that still remains to be understood.…”

CD44 Glycosylation as a Therapeutic Target in Oncology

“…Why does truncation of CD44 O-glycosylation contribute to downstream signaling? We speculate that excessive O-glycosylation, similar to incomplete O-glycosylation of CD44, affects the efficiency of CD44 function ( 68 – 71 ). Furthermore, the increased tumorigenicity of pancreatic cancer caused by knockdown of C1GalT1 may be also related to the truncation of o-glycosylation on MUC16 ( 69 ).…”

“…C1GalT1 is overexpressed in many cancers of epithelial origin, including colon, breast, gastric, HNSCC, esophagus, prostate, and hepatocellular carcinoma. C1GalT1 overexpression is also frequently associated with poorer prognosis and poorer patient survival ( 68 ). The oncogenic effects of C1GalT1 may be achieved by altering the glycosylation and function of receptor tyrosine kinases, cell surface integrins, and cell surface death receptors ( 68 ).…”

“…C1GalT1 overexpression is also frequently associated with poorer prognosis and poorer patient survival ( 68 ). The oncogenic effects of C1GalT1 may be achieved by altering the glycosylation and function of receptor tyrosine kinases, cell surface integrins, and cell surface death receptors ( 68 ). However, human pancreatic cancer cells with knockout of C1GALT1 had an increased tendency for tumorigenesis and metastasis ( 69 ).…”

Galectins in Esophageal Cancer: Current Knowledge and Future Perspectives

“…This was linked to altered glycosylation of β1-integrin, another known ligand of different galectins [ 86 , 87 , 88 , 89 ]. Based on these examples, it can be anticipated that—similar to other cancers [ 10 , 90 ]—altered tumor cell glycosylation in combination with altered galectin expression contributes to tumor progression in esophageal cancer [ 91 ]. This warrants further studies into the (aberrant) mechanisms of glycosylation in esophageal cancer by, e.g., more extensive glycan profiling and analysis of the expression/function of enzymes involved in the glycosylation machinery.…”