Type

Journal Article

Authors

Pauline M Rudd
Amanda McCann
Rosa Peracaula
Stephen F Madden
David J Harvey
Weston B Struwe
Alfonso Blanco Fernández
Jenny A Watson
Karina Mariño
Marta Pérez-Garay
and 2 others

Subjects

Biochemistry

Topics
glycoproteins female neoplasms glandular and epithelial genetics methylation metabolism glycosyltransferases polysaccharides azacitidine decitabine ovarian neoplasms glycosylation analogs derivatives humans

5-AZA-2'-deoxycytidine induced demethylation influences N-glycosylation of secreted glycoproteins in ovarian cancer. (2011)

Abstract Glycosylation is the most common posttranslational modification of proteins and is highly reflective of changes in the environment of a cell. Epigenetic modifications to the genome are stably transmitted to daughter cells without the requirement for genetic sequence alterations. Aberrant regulation of both epigenetic programming and glycosylation patterning are integral aspects of carcinogenesis. The objective of this study was to determine the interplay between these two complex cellular processes. We demonstrate that global DNA methylation changes in ovarian cancer epithelial cells (OVCAR3) resulted in significant alterations in the glycosylation of secreted glycoproteins. These changes included a reduction in core fucosylation, increased branching and increased sialylation. We further show that the change in core fucose levels was mirrored by altered expression of GMDS and FX, key enzymes in fucose biosynthesis. Alterations in the expression of key glycosyltransferase enzymes such as MGAT5 reflect the changes seen in the branching and sialylation of secreted glycans. Overall, our results highlight that modifications to the epigenetic 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 cancer progression.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Pauline M Rudd, Amanda McCann, Rosa Peracaula, Stephen F Madden, David J Harvey, Weston B Struwe, Alfonso Blanco Fernández, Jenny A Watson, Karina Mariño, Marta Pérez-Garay and 2 others

Experts in our system

1
Pauline M Rudd
University College Dublin
Total Publications: 45
 
2
Amanda McCann
University College Dublin
Total Publications: 41
 
3
Stephen F Madden
Dublin City University
Total Publications: 45
 
4
Jenny A Watson
University College Dublin
Total Publications: 8