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Polysialic acid sustains cancer cell survival and migratory capacity in a hypoxic environment
Elkashef, Sara M. Allison, Simon J. Sadiq, Maria Basheer, Haneen A. Ribeiro Morais, Goreti Pors, Klaus Falconer, Robert A.
Elkashef, Sara M.
Allison, Simon J.
Sadiq, Maria
Basheer, Haneen A.
Ribeiro Morais, Goreti
Pors, Klaus
Falconer, Robert A.
Publication Date
2016-09
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© The Author(s) 2016. This work is licensed under a Creative Commons
Attribution 4.0 International License. The images or other third party material in this article are
included in the article’s Creative Commons license, unless indicated otherwise in the credit line;
if the material is not included under the Creative Commons license, users will need to obtain
permission from the license holder to reproduce the material. To view a copy of this license, visit
http://creativecommons.org/licenses/by/4.0/
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openAccess
Accepted for publication
15/08/2016
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Abstract
Polysialic acid (polySia) is a unique carbohydrate polymer expressed on the surface of NCAM (neuronal
cell adhesion molecule) in a number of cancers where it modulates cell-cell and cell-matrix adhesion,
migration, invasion and metastasis and is strongly associated with poor clinical prognosis. We have
carried out the first investigation into the effect of polySia expression on the behaviour of cancer cells
in hypoxia, a key source of chemoresistance in tumours. The role of polysialylation and associated
tumour cell migration and cell adhesion were studied in hypoxia, along with effects on cell survival
and the potential role of HIF-1. Our findings provide the first evidence that polySia expression
sustains migratory capacity and is associated with tumour cell survival in hypoxia. Initial mechanistic
studies indicate a potential role for HIF-1 in sustaining polySia-mediated migratory capacity, but
not cell survival. These data add to the growing body of evidence pointing to a crucial role for the
polysialyltransferases (polySTs) in neuroendocrine tumour progression and provide the first evidence to
suggest that polySia is associated with an aggressive phenotype in tumour hypoxia. These results have
significant potential implications for polyST inhibition as an anti-metastatic therapeutic strategy and
for targeting hypoxic cancer cells.
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Published version
Citation
Elkashef SM, Allison SJ, Sadiq M et al. (2016) Polysialic acid sustains cancer cell survival
and migratory capacity in a hypoxic environment. Scientific Reports. 6: Article number 33026.
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Article