Yes / 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. / This 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).
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/8980 |
| Date | 09 September 2016 |
| Creators | Elkashef, Sara M., Allison, Simon J., Sadiq, Maria, Basheer, Haneen A., Ribeiro Morais, Goreti, Loadman, Paul, Pors, Klaus, Falconer, Robert A. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, published version |
| 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/ |
Page generated in 0.0017 seconds