Polysialyltransferase: a new target in metastatic cancer.

  title={Polysialyltransferase: a new target in metastatic cancer.},
  author={Robert A. Falconer and Rachel J. Errington and Steven D. Shnyder and P. J. Smith and Laurence H. 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… 

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.

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.

Antibody-MediatedEndocytosis of PolysialicAcid Enables IntracellularDeliveryandCytotoxicityofa Glycan-Directed Antibody–Drug Conjugate

These 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.

Polysialic acid: Biosynthesis, novel functions and applications

Bacterial polysialyltransferases are more promiscuous than the protein-specific mammalian enzymes, and new studies suggest that these enzymes have tremendous therapeutic potential, especially for strategies aimed at neural regeneration and tissue repair.

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.

A new strategy for identifying polysialylated proteins reveals they are secreted from cancer cells as soluble proteins and as part of extracellular vesicles

The secretion of polysialic acid on both soluble and EV-associated proteins from MCF-7 cancer cells is reported and a new method to efficiently identifypolysialylated proteins is introduced, which has exciting implications for understanding the roles of polySia in cancer progression and metastasis and for identifying new cancer biomarkers.

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.

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.

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.