5-AZA-2'-deoxycytidine induced demethylation influences N-glycosylation of secreted glycoproteins in ovarian cancer

SALDOVA, RADKA; DEMPSEY, EUGENE; PEREZ-GARAY, MARTA; MARIÑO, KARINA; WATSON, JENNY A.; BLANCO FERNANDEZ, A.; STRUWE, W.B; HARVEY, DAVID H.; MADDEN, S.F.; PERACAULA, ROSA; MC CANN, AMANDA; RUDD, PAULINE M

EPIGENETICS

LANDES BIOSCIENCE

Año: 2011

1559-2294

Glycosylation is the most common posttranslational modification of proteins and is highlyreflective of changes in the environment of a cell. Epigenetic modifications to the genomeare stably transmitted to daughter cells without the requirement for genetic sequencealterations. Aberrant regulation of both epigenetic programming and glycosylationpatterning are integral aspects of carcinogenesis. The objective of this study was todetermine the interplay between these two complex cellular processes. We demonstratethat global DNA methylation changes in ovarian cancer epithelial cells (OVCAR3) resulted insignificant alterations in the glycosylation of secreted glycoproteins. These changes includeda reduction in core fucosylation, increased branching and increased sialylation. We furthershow that the change in core fucose levels was mirrored by altered expression of GMDS andFX, key enzymes in fucose biosynthesis. Alterations in the expression of keyglycosyltransferase enzymes such as MGAT5 reflect the changes seen in the branching andsialylation of secreted glycans. Overall, our results highlight that modifications to theepigenetic machinery have a profound effect on the glycan structures generated by cells,which may be a key step in understanding metastasis and drug resistance during cancerprogression.