Highlights d MYC directly induces the transcription of D2HGDH and L2HGDH d The MYC D2HGDH/L2HGDH interplay influences intermediary metabolism d The MYC-D2HGDH/L2HGDH axis activates TET and RNA demethylases d MYC-expressing B cell lymphomas display hypomethylated and active enhancers
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.
Highlights Polysialic acid is of significant interest due its roles in biology and disease First systematic review of approaches for extraction and characterisation of polysialic acids from biological matrices Approaches to analysis of the degree of polymerisation of polysialic acid evaluated Quantitation considered, including accuracy and limit of detection
Bradford Scholars -how to deposit your paper
Overview
Copyright check• Check if your publisher allows submission to a repository.• Use the Sherpa RoMEO database if you are not sure about your publisher's position or email openaccess@bradford.ac.uk.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.