Journal
EPIGENETICS
Volume 11, Issue 12, Pages 845-857Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15592294.2016.1241932
Keywords
Chemo-resistance; epigenetics; epigenetic therapies; hypoxia N-glycosylation
Funding
- Science foundation Ireland Starting Investigator Research grant (SFI SIRG) [13/SIRG/2164]
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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.
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