Polysialyltransferase: a new target in metastatic cancer.

  title={Polysialyltransferase: a new target in metastatic cancer.},
  author={R. Falconer and R. Errington and S. Shnyder and P. Smith and L. Patterson},
  journal={Current cancer drug targets},
  volume={12 8},
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… Expand
Pharmacological Inhibition of polysialyltransferase ST8SiaII Modulates Tumour Cell Migration
ST8SiaII can be considered a druggable target with the potential for interfering with a critical mechanism in tumour cell dissemination in metastatic cancers, and is demonstrated for the first time that a polysialyltransferase inhibitor can modulate migration in ST8SIAII-expressing tumour cells. Expand
Polysialic acid sustains cancer cell survival and migratory capacity in a hypoxic environment
These findings provide the first evidence that polySia expression sustains migratory capacity and is associated with tumour cell survival in hypoxia, and have significant potential implications for polyST inhibition as an anti-metastatic therapeutic strategy and for targeting hypoxic cancer cells. Expand
Polysialic acid: Biosynthesis, novel functions and applications
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The Inhibition of Polysialyltranseferase ST8SiaIV through Heparin binding to Polysialyltransferase Domain (PSTD).
The findings in the present study demonstrate that PSTD domain is a potential target of heparin and may provide new insights into the molecular rationale ofheparin-inhibiting NCAM polysialylation. Expand
Recent advances in the analysis of polysialic acid from complex biological systems.
Analytical approaches used for the determination of polySia in biological matrices in the past 20 years are discussed, with a particular focus on chemical approaches, and quantitative analysis. Expand
Antibody-Mediated Endocytosis of Polysialic Acid Enables Intracellular Delivery and Cytotoxicity of a Glycan-Directed Antibody-Drug Conjugate.
Results establish polySia as a valid cell-surface, cancer-specific target for glycan-directed ADC and contribute to a growing body of evidence that the tumor glycocalyx is a promising target for synthetic immunotherapies. Expand
The Polybasic Region of the Polysialyltransferase ST8Sia-IV Binds Directly to the Neural Cell Adhesion Molecule, NCAM.
NMR titration experiments verified the role of the FN1 acidic patch in the recognition of the PBR and suggest a conformational change of the Ig5-FN1 linker region following binding of thePBR to the acidic patch. Expand
The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C
The structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries. Expand
The Effect of Polysialic Acid Expression on Glioma Cell Nano-mechanics
It is demonstrated that polySia expression leads to reduced elastic and adhesive properties but also more viscoelastic compared to non-expressing wild-type cells, whilst differences in cell elasticity between healthy and cancer cells are regularly assigned to changes in the cytoskeleton. Expand
Effects of the regulation of polysialyltransferase ST8SiaII on the invasiveness and metastasis of small cell lung cancer cells.
Polysialic acid-modified NCAM on the surface of SCLC cells is closely related to the metastatic potential of these cells; regulation of ST8SiaII may affect the invasiveness and metastasis of SclC, and these processes may be associated with phosphorylation of FGFR1, ERK1/2 or MMP-9. Expand