In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 2423-2423
Abstract:
Glycosylation, one of the most fundamental post-translational modifications, is altered in many cancers. These alterations have been proven to impact on the progression of the tumor cell and promote survival. In literature published over the last half century, it is obvious there is a clear link between (a) chemo-resistance and hypoxia (b) hypoxia and epigenetics and more recently (c) glycosylation and epigenetics. We aim to bring these paradigms together with the remit of offering a more complete story and opening up new avenues of approach for the detection, diagnosis and treatment of breast and ovarian cancer. Ovarian and breast cancer cells were exposed to differential hypoxic conditions (0.5%, 1.0%, 2.0%) and normoxia. Firstly, we compared the methylation status of hypoxia exposed cells to the normoxic controls. A combination of hydrophilic interaction liquid chromatography (HILIC) and statistical analyses allowed comparisons of the secreted N-glycans from cells exposed to differential hypoxic conditions. Western blots assessed apoptosis, senescence, autophagy and epithelial to mesenchymal transition. The OrisTM migration assay assessed the migration of the cells pre- and post-differential hypoxic exposure. RT-qPCR was used to measure gene expression of appropriate glycosyltransferases and possible transcription factors (TFs) in these samples to determine any associations with changes seen in N-glycosylation. There were non-significant trends observed between the percentage oxygen that the cells were exposed to and resultant changes seen in branching and sialylation on secreted N-glycans from the breast and ovarian cancer cell lines. While only some of these changes could be explained by RT-qPCR data, GATA2/3 transcripts, identified in-silico as possible TFs, have been shown to significantly correlate with ST3GAL4 and MGAT5 glycosyltransferases, respectively. Hypoxia exposed cells also displayed increased migration with a greater effect seen in the 0.5% hypoxia exposed samples. The GATA2 and GATA3 transcription factors are gaining popularity in recent years, with links to cancer stage, increased invasiveness and as possible therapeutic targets. Our recent data shows a strong correlation between GATA2 and GATA3 and the levels of glycosyltransferases involved in branching and sialyation. These glycan changes are known to be strongly involved in cancer cell survival and metastases. Here for the first time we may have a possible mechanism of action linking GATA2 and 3 and invasiveness of breast and ovarian cancer cells. Citation Format: Gordon Greville, Esther Llop, Rosa Peracaula Miró, Amanda McCann, Pauline M. Rudd, Radka Saldova. Hypoxia regulates tumor cell invasiveness through altered glycosylation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2423.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2018-2423
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2018
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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