Polysialyltransferase: A New Target in Metastatic Cancer

Falconer, Robert A.; Errington, Rachel J.; Shnyder, Steve D.; Smith, Pamela J. Olúbùnmi; Patterson, Laurence H.

doi:10.2174/156800912803251225

Cited by 96 publications

(115 citation statements)

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“…Increased sialylation in cancer also includes the expression of polysialic acid, which is associated with several types of cancers and is frequently expressed in high-grade tumours 51,52 . Polysialic acid can often be present in neural cell adhesion molecule 1 (NCAM1), and this is associated with aggressiveness and poor clinical outcome in cancers, including lung cancer, neuroblastoma and gliomas 51,52 .…”

Section: Sialylationmentioning

confidence: 99%

Glycosylation in cancer: mechanisms and clinical implications

2015

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Despite recent progress in understanding the cancer genome, there is still a relative delay in understanding the full aspects of the glycome and glycoproteome of cancer. Glycobiology has been instrumental in relevant discoveries in various biological and medical fields, and has contributed to the deciphering of several human diseases. Glycans are involved in fundamental molecular and cell biology processes occurring in cancer, such as cell signalling and communication, tumour cell dissociation and invasion, cell-matrix interactions, tumour angiogenesis, immune modulation and metastasis formation. The roles of glycans in cancer have been highlighted by the fact that alterations in glycosylation regulate the development and progression of cancer, serving as important biomarkers and providing a set of specific targets for therapeutic intervention. This Review discusses the role of glycans in fundamental mechanisms controlling cancer development and progression, and their applications in oncology.

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Section: Sialylationmentioning

confidence: 99%

Glycosylation in cancer: mechanisms and clinical implications

2015

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“…Its biosynthesis is regulated by polysialyltransferases. It has been found that polysialic acid is also aberrantly re-expressed on the surface of many tumors, where it plays a key role in disease progression and metastasis [34]. Therefore, polysialyltransferases have been also considered as an attractive anti-cancer drug target.…”

Section: Cytidine Analogsmentioning

confidence: 99%

Sialyltransferase inhibition and recent advances

Wang

Liu

et al. 2016

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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Sialic acids, existing as terminal sugars of glycoconjugates, play important roles in various physiological and pathological processes, such as cell-cell adhesion, immune defense, tumor cell metastasis, and inflammation. Sialyltransferases (STs) catalyze the transfer of sialic acid residues to non-reducing oligosaccharide chains of proteins and lipids, using cytidine monophosphate N-acetylneuraminic acid (CMP-Neu5Ac) as the donor. Elevated sialyltransferase activity leads to overexpression of cell surface sialic acids and contributes to many disease developments, such as cancer and inflammation. Therefore, sialyltransferases are considered as potential drug targets for disease treatment. Inhibitors of sialyltransferases thus are of medicinal interest, especially for the cancer therapy. In addition, sialyltransferase inhibitors are useful tool to study sialyltransferase function and related mechanisms. This review highlights recent development of inhibitors of sialyltransferases reported since 2004. The inhibitors are summarized as eight groups: 1) sialic acid analogs, 2) CMP-sialic acid analogs, 3) cytidine analogs, 4) oligosaccharide derivatives, 5) aromatic compounds, 6) flavonoids, 7) lithocholic acid analogs, and 8) others. This article is part of a Special Issue entitled: Physiological Enzymology and Protein Functions.

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“…From a clinical standpoint, changes in polySia expression have been observed in neurological disorders such as schizophrenia 9 . Likewise, polySia overexpression has been linked to the malignant potential of numerous tumors including neuroendocrine tumors, Wilms' tumor, neuroblastoma, colon cancer and pancreatic cancer 10 . However, despite these multifaceted roles in human biology and disease, the enzymes that mediate these critical posttranslational modifications, the polysialyl transferases, have remained uncharacterized at the molecular level.…”

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confidence: 99%

Structure of human ST8SiaIII sialyltransferase provides insight into cell-surface polysialylation

Volkers

Worrall

Kwan

et al. 2015

Nat Struct Mol Biol

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Sialyltransferases of the mammalian ST8Sia family catalyze oligo- and polysialylation of surface-localized glycoproteins and glycolipids through transfer of sialic acids from CMP-sialic acid to the nonreducing ends of sialic acid acceptors. The crystal structure of human ST8SiaIII at 1.85-Å resolution presented here is, to our knowledge, the first solved structure of a polysialyltransferase from any species, and it reveals a cluster of polysialyltransferase-specific structural motifs that collectively provide an extended electropositive surface groove for binding of oligo-polysialic acid chain products. The ternary complex of ST8SiaIII with a donor sugar analog and a sulfated glycan acceptor identified with a sialyltransferase glycan array provides insight into the residues involved in substrate binding, specificity and sialyl transfer.

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Polysialyltransferase: A New Target in Metastatic Cancer

Cited by 96 publications

References 0 publications

Glycosylation in cancer: mechanisms and clinical implications

Glycosylation in cancer: mechanisms and clinical implications

Sialyltransferase inhibition and recent advances

Structure of human ST8SiaIII sialyltransferase provides insight into cell-surface polysialylation

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