Polysialyltransferase: a new target in metastatic cancer

Polysialic acid (polySia) is a carbohydrate polymer critical for neuronal cell migration and axon pathfinding in embryonic development. Besides brain regions requiring persistent neuronal plasticity, polySia is essentially absent from the adult body. However, polySia is aberrantly re-expressed on many tumours, where it decorates the surface of NCAM (neuronal cell adhesion molecule) and modulates cell adhesion, migration and invasion. PolySia-NCAM expression is strongly associated with poor clinical prognosis and correlates with aggressive and invasive disease in many cancers, including lung cancer, neuroblastoma and gliomas. The synthesis of polySia is mediated by two polysialyltransferases (polySTs), ST8SiaIV (PST) and particularly ST8SiaII (STX) in cancer cells. The demonstration that polyST knock-down negates events associated with tumour cell dissemination indicates that PST and STX are validated targets. Selective inhibition of polySTs therefore presents a therapeutic opportunity to inhibit tumour invasion and metastasis.