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

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Authors
Alam, Shahidul
Anugraham, Merrina
Huang, Yen-Lin
Kohler, Reto
Winkelbach, Katharina
Nunez Lopez, Monica
Khasbiullina, Nailia
Bovin, Nicolai V.
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Publication date
30.03.2017
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01A - Journal article
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Scientific Reports
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7
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45367
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Abstract
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.
Keywords
lacto series, glycolipid, biosynthesis
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2045-2322
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English
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Yes
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Published
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ALAM, Shahidul, Merrina ANUGRAHAM, Yen-Lin HUANG, Reto KOHLER, Timm HETTICH, Katharina WINKELBACH, Yasmin GRETHER, Monica NUNEZ LOPEZ, Nailia KHASBIULLINA, Nicolai V. BOVIN, Götz SCHLOTTERBECK und Francis JACOB, 2017. Altered (neo-) lacto series glycolipid biosynthesis impairs α2-6 sialylation on N-glycoproteins in ovarian cancer cells. Scientific Reports. 30 März 2017. Bd. 7, S. 45367. DOI 10.1038/srep45367. Verfügbar unter: http://hdl.handle.net/11654/25891