Altered (neo-) lacto series glycolipid biosynthesis impairs α2-6 sialylation on N-glycoproteins in ovarian cancer cells

The (neo-) lacto series glycosphingolipids (nsGSLs) comprise of glycan epitopes that are present as blood group antigens, act as primary receptors for human pathogens and are also increasingly associated with malignant diseases. Beta-1, 3- N -acetyl-glucosaminyl-transferase 5 (B3GNT5) is suggested a...

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Published in:Scientific reports 2017-03, Vol.7 (1), p.45367-45367, Article 45367
Main Authors: Alam, Shahidul, Anugraham, Merrina, Huang, Yen-Lin, Kohler, Reto S., Hettich, Timm, Winkelbach, Katharina, Grether, Yasmin, López, Mónica Núñez, Khasbiullina, Nailia, Bovin, Nicolai V., Schlotterbeck, Götz, Jacob, Francis
Format: Article
Language:English
Subjects:
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13/1
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14/1
14/63
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631/45/1268
631/45/221
631/80/221
Cell Line, Tumor
CRISPR-Cas Systems
Female
Gene Knockout Techniques
Glycomics
Glycoproteins - metabolism
Glycosphingolipids - metabolism
HeLa Cells
Humanities and Social Sciences
Humans
multidisciplinary
N-Acetylgalactosaminyltransferases - genetics
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Science
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Summary:The (neo-) lacto series glycosphingolipids (nsGSLs) comprise of glycan epitopes that are present as blood group antigens, act as primary receptors for human pathogens and are also increasingly associated with malignant diseases. Beta-1, 3- N -acetyl-glucosaminyl-transferase 5 (B3GNT5) is suggested as the key glycosyltransferase for the biosynthesis of nsGSLs. In this study, we investigated the impact of CRISPR- Cas9 -mediated gene disruption of B3GNT5 (∆ B3GNT5 ) on the expression of glycosphingolipids and N -glycoproteins by utilizing immunostaining and glycomics-based PGC-UHPLC-ESI-QTOF-MS/MS profiling. ∆ B3GNT5 cells lost nsGSL expression coinciding with reduction of α2-6 sialylation on N -glycoproteins. In contrast, disruption of B4GALNT1 , a glycosyltransferase for ganglio series GSLs did not affect α2-6 sialylation on N -glycoproteins. We further profiled all known α2-6 sialyltransferase-encoding genes and showed that the loss of α2-6 sialylation is due to silencing of ST6GAL1 expression in ∆ B3GNT5 cells. These results demonstrate that nsGSLs are part of a complex network affecting N -glycosylation in ovarian cancer cells.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep45367