title: Suppression of core 1 Gal-transferase is associated with reduction of TF and reciprocal increase of Tn, sialyl-Tn and Core 3 glycans in human colon cancer cells.
abstract: It has long been presumed, though with surprisingly little evidence, a competition between Core 1 Gal-transferase (C1GalT), Core 3 GlcNAc-transferase (C3GnT) and sialyl-transferase (ST6GalNAc-T) for elongation of O-linked mucin-type glycans initiated with GalNAcα-Ser/Thr. This study tested this presumption by selective suppression of one of these glycosyltransferases and then analysed the expressions of the enzymatic products of the other three glycosyltransferases. It was found that siRNA suppression of C1GalT markedly reduced the expression of Galβ1,3GalNAcα- (Core 1) and in the meantime increased the expressions of sialyl-GalNAcα- (sialyl-Tn), GalNAcα- (Tn) and GlcNAcβ1,3GalNAcα- (Core 3)-associated glycans in human colon cancer HT29 and SW620 cells. This supports a competitive modification of the GalNAcα-Ser/Thr between C1GalT, C3GnT and ST6GalNAc-T in O-glycan biosynthesis. As Tn, TF and sialyl-Tn are oncofetal antigens and are over-expressed in most human cancers, this information is useful for the development of glycosyltransferase-targeted therapeutic strategies for cancer treatment.
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Hannah
authors.initials: H
authors.lastname: Barrow
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tam
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Duckworth
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Rhodes
authors.forename: Lu-Gang
authors.initials: LG
authors.lastname: Yu
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D005700:Galactosyltransferases / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D009077:Mucins / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D009077:Mucins; D011134:Polysaccharides; C040286:Tn antigen; C055491:sialosyl-Tn antigen; C016467:Thomsen-Friedenreich antigen; C505293:C1GALT1 protein, human; D005700:Galactosyltransferases
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