Epigenetic regulation of glycosylation and the impact on chemo-resistance in breast and ovarian cancer.
Glycosylation is one of the most fundamental posttranslational modifications in cellular biology and has been shown to be epigenetically regulated. Understanding this process is important as epigenetic therapies such as those using DNA methyltransferase inhibitors are undergoing clinical trials for the treatment of ovarian and breast cancer. Previous work has demonstrated that altered glycosylation patterns are associated with aggressive disease in women presenting with breast and ovarian cancer. Moreover, the tumor microenvironment of hypoxia results in globally altered DNA methylation and is associated with aggressive cancer phenotypes and chemo-resistance, a feature integral to many cancers. There is sparse knowledge on the impact of these therapies on glycosylation. Moreover, little is known about the efficacy of DNA methyltransferase inhibitors in hypoxic tumors. In this review, we interrogate the impact that hypoxia and epigenetic regulation has on cancer cell glycosylation in relation to resultant tumor cell aggressiveness and chemo-resistance.
a NIBRT GlycoScience Group , The National Institute for Bioprocessing Research and Training , Mount Merrion, Blackrock, Dublin , Ireland.
Gordon
G
Greville
b UCD School of Medicine, College of Health and Agricultural Science, University College Dublin , UCD, Belfield, Dublin , Ireland.|c UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , UCD, Belfield, Dublin , Ireland.
Amanda
A
McCann
a NIBRT GlycoScience Group , The National Institute for Bioprocessing Research and Training , Mount Merrion, Blackrock, Dublin , Ireland.
Pauline M
PM
Rudd
a NIBRT GlycoScience Group , The National Institute for Bioprocessing Research and Training , Mount Merrion, Blackrock, Dublin , Ireland.
Radka
R
Saldova
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006031:Glycosylation; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
D004791:Enzyme Inhibitors; D015254:DNA Modification Methylases
Chemo-resistance; N-glycosylation; epigenetic therapies; epigenetics; hypoxia
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