Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.99.6 (sialyltransferase)
 1,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sialyl-Tn is a carbohydrate antigen overexpressed in several epithelial cancers, including breast cancer, and usually associated with poor prognosis. Sialyl-Tn is synthesized by a CMP-Neu5Ac:GalNAcalpha2,6-sialyltransferase: CMP-Neu5Ac: R-GalNAcalpha1-O-Ser/Thr alpha2,6-sialyltransferase (EC 2.4.99.3) (ST6GalNAc I), which transfers a sialic acid residue in alpha2,6-linkage to the GalNAcalpha1-O-Ser/Thr structure. However, established breast cancer cell lines express neither ST6GalNAc I nor sialyl-Tn. We have previously shown that stable transfection of MDA-MB-231, a human breast cancer cell line, with ST6GalNAc I cDNA induces sialyl-Tn antigen (STn) expression. We report here the modifications of the O-glycosylation pattern of a MUC1-related recombinant protein secreted by MDA-MB-231 sialyl-Tn positive cells. We also show that sialyl-Tn expression and concomitant changes in the overall O-glycan profiles induce a decrease of adhesion and an increase of migration of MDA-MB-231. Moreover, STn positive clones exhibit an increased tumour growth in severe combined immunodeficiency (SCID) mice. These observations suggest that modification of the O-glycosylation pattern induced by ST6GalNAc I expression are sufficient to enhance the tumourigenicity of MDA-MB-231 breast cancer cells.
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PMID:ST6GalNAc I expression in MDA-MB-231 breast cancer cells greatly modifies their O-glycosylation pattern and enhances their tumourigenicity. 1613 58

Research using mouse lymphoma cell lines has resulted in many reports of glycosylation being a key regulator for the distant metastasis of mouse lymphoma cells in animal models. In contrast, there are only a few reports of experiments examining human lymphoma cell metastasis. The glycosylation pattern in human lymphoma shows that loss of Phaseolus vulgaris leukoagglutinating lectin (L-PHA) reactive oligosaccharides, and sialylation of L-PHA reactive oligosaccharides, are closely associated with a worse prognosis for diffuse large B cell lymphoma (DLBCL) patients. Sialic acid is related to cell adhesion to the extracellular matrix and metastasis of HBL-8 Burkitt lymphoma cells in a severe combined immunodeficiency (SCID) mouse animal model. In HBL-8 clones, differential cell surface sialylation was due to different expression levels of UDP-GlcNAc 2-epimerase (GNE). Knockdown of beta-galactoside alpha-2,6-sialyltransferase (ST6Gal1) resulted in enhanced lymphoma cell adhesion to galectin-1 in anaplastic large cell lymphoma cell line, H-ALCL. A fluorinated sialic acid analogue was shown to be useful for inhibiting sialyltransferase and may provide a new glycoengineering strategy for desialylation, as well as inhibiting invasion and metastasis and inducing cell death in lymphoma cell lines. This paper discusses glycosylation and sialylation in human lymphoma, and several glycoengineering therapeutic strategies for lymphoma.
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PMID:Glycosylation in lymphoma: Biology and glycotherapy. 3131 21