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

被引:26
作者
Barrow, Hannah [1 ]
Tam, Benjamin [1 ]
Duckworth, Carrie A. [1 ]
Rhodes, Jonathan M. [1 ]
Yu, Lu-Gang [1 ]
机构
[1] Univ Liverpool, Inst Translat Med, Dept Gastroenterol, Liverpool L69 3BX, Merseyside, England
来源
PLOS ONE | 2013年 / 8卷 / 03期
关键词
FRIEDENREICH CARBOHYDRATE ANTIGEN; O-GLYCOSYLATION; BREAST-CANCER; ACETYLGALACTOSAMINYLTRANSFERASE FAMILY; CIRCULATING GALECTIN-3; PROTEIN GLYCOSYLATION; COLORECTAL-CANCER; GOLGI-APPARATUS; CARCINOMA-CELLS; GENE FAMILY;
D O I
10.1371/journal.pone.0059792
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 GalNAc alpha-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 Gal beta 1,3GalNAc alpha- (Core 1) and in the meantime increased the expressions of sialyl-GalNAc alpha- (sialyl-Tn), GalNAc alpha- (Tn) and GlcNAc beta 1,3GalNAc alpha-(Core 3)-associated glycans in human colon cancer HT29 and SW620 cells. This supports a competitive modification of the GalNAc alpha-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.
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页数:6
相关论文
共 44 条
[1]   Serum Galectin-2,-4, and -8 Are Greatly Increased in Colon and Breast Cancer Patients and Promote Cancer Cell Adhesion to Blood Vascular Endothelium [J].
Barrow, Hannah ;
Guo, Xiuli ;
Wandall, Hans H. ;
Pedersen, Johannes W. ;
Fu, Bo ;
Zhao, Qicheng ;
Chen, Chen ;
Rhodes, Jonathan M. ;
Yu, Lu-Gang .
CLINICAL CANCER RESEARCH, 2011, 17 (22) :7035-7046
[2]   The role of galectins in colorectal cancer progression [J].
Barrow, Hannah ;
Rhodes, Jonathan M. ;
Yu, Lu-Gang .
INTERNATIONAL JOURNAL OF CANCER, 2011, 129 (01) :1-8
[3]   Control of mucin-type O-glycosylation: A classification of the polypeptide GalNAc-transferase gene family [J].
Bennett, Eric P. ;
Mandel, Ulla ;
Clausen, Henrik ;
Gerken, Thomas A. ;
Fritz, Timothy A. ;
Tabak, Lawrence A. .
GLYCOBIOLOGY, 2012, 22 (06) :736-756
[4]   Effect of N-glycosylation on turnover and subcellular distribution of N-acetylgalactosaminyltransferase I and sialyltransferase II in neuroblastoma cells [J].
Bieberich, E ;
Tencomnao, T ;
Kapitonov, D ;
Yu, RK .
JOURNAL OF NEUROCHEMISTRY, 2000, 74 (06) :2359-2364
[5]   Pathways of O-glycan biosynthesis in cancer cells [J].
Brockhausen, I .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1999, 1473 (01) :67-95
[6]  
Brockhausen I, 2009, ESSENTIALS GLYCOBIOL
[7]  
Campbell B, 2001, SMITHSONIAN, V32, P18
[8]   Tumour-associated carbohydrate antigens in breast cancer [J].
Cazet, Aurelie ;
Julien, Sylvain ;
Bobowski, Marie ;
Burchell, Joy ;
Delannoy, Philippe .
BREAST CANCER RESEARCH, 2010, 12 (03)
[9]   The roles of enzyme localisation and complex formation in glycan assembly within the Golgi apparatus [J].
de Graffenried, CL ;
Bertozzi, CR .
CURRENT OPINION IN CELL BIOLOGY, 2004, 16 (04) :356-363
[10]   Anti-Thomsen-Friedenreich (T) antibody-based ELISA and its application to human breast carcinoma detection [J].
Desai, PR ;
Ujjainwala, LH ;
Carlstedt, SC ;
Springer, GF .
JOURNAL OF IMMUNOLOGICAL METHODS, 1995, 188 (02) :175-185