Show simple item record

dc.contributor.authorElkashef, Sara M.*
dc.contributor.authorAllison, Simon J.*
dc.contributor.authorSadiq, Maria*
dc.contributor.authorBasheer, Haneen A.*
dc.contributor.authorRibeiro Morais, Goreti*
dc.contributor.authorLoadman, Paul M.*
dc.contributor.authorPors, Klaus*
dc.contributor.authorFalconer, Robert A.*
dc.date.accessioned2016-09-14T10:52:45Z
dc.date.available2016-09-14T10:52:45Z
dc.date.issued2016-09
dc.identifier.citationElkashef 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.en_US
dc.identifier.urihttp://hdl.handle.net/10454/8980
dc.descriptionYesen_US
dc.description.abstractPolysialic 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.en_US
dc.description.sponsorshipThis work was primarily supported by a PhD studentship for SME (RAF) and partly by Yorkshire Cancer Research (PML, KP, RAF), a Prostate Cancer UK studentship for MS (KP) and a Wellcome Trust grant (RAF).en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1038/srep33026en_US
dc.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/en_US
dc.subjectPolysialic acid; polySia; Cancer cells; Hypoxiaen_US
dc.titlePolysialic acid sustains cancer cell survival and migratory capacity in a hypoxic environmenten_US
dc.status.refereedYesen_US
dc.date.Accepted2016-08-15
dc.date.application2016-09-09
dc.typeArticleen_US
dc.type.versionpublished versionen_US
refterms.dateFOA2018-07-25T14:07:54Z


Item file(s)

Thumbnail
Name:
Falconer_Scientific_Reports.pdf
Size:
1.207Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record