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    Polysialic acid sustains cancer cell survival and migratory capacity in a hypoxic environment

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    Falconer_Scientific_Reports.pdf (1.207Mb)
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    Publication date
    2016-09
    Author
    Elkashef, Sara M.
    Allison, Simon J.
    Sadiq, Maria
    Basheer, Haneen A.
    Ribeiro Morais, Goreti
    Loadman, Paul M.
    Pors, Klaus
    Falconer, Robert A.
    Keyword
    Polysialic acid; polySia; Cancer cells; Hypoxia
    Rights
    © 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/
    Peer-Reviewed
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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.
    URI
    http://hdl.handle.net/10454/8980
    Version
    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.
    Link to publisher’s version
    http://dx.doi.org/10.1038/srep33026
    Type
    Article
    Collections
    Life Sciences Publications

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