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      ST6GAL1: A key player in cancer

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          Abstract

          Aberrant glycosylation is a universal feature of cancer cells and there is now overwhelming evidence that glycans can modulate pathways intrinsic to tumour cell biology. Glycans are important in all of the cancer hallmarks and there is a renewed interest in the glycomic profiling of tumours to improve early diagnosis, determine patient prognosis and identify targets for therapeutic intervention. One of the most widely occurring cancer associated changes in glycosylation is abnormal sialylation which is often accompanied by changes in sialyltransferase activity. Several sialyltransferases are implicated in cancer, but in recent years ST6 β-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) has become increasingly dominant in the literature. ST6GAL1 catalyses the addition of α2,6-linked sialic acids to terminal N-glycans and can modify glycoproteins and/or glycolipids. ST6GAL1 is upregulated in numerous types of cancer (including pancreatic, prostate, breast and ovarian cancer) and can promote growth, survival and metastasis. The present review discusses ST6GAL in relation to the hallmarks of cancer, and highlights its key role in multiple mechanisms intrinsic to tumour cell biology.

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          PI3K: Downstream AKTion Blocks Apoptosis

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            Hallmarks of glycosylation in cancer

            Aberrant glycosylation plays a fundamental role in key pathological steps of tumour development and progression. Glycans have roles in cancer cell signalling, tumour cell dissociation and invasion, cell-matrix interactions, angiogenesis, metastasis and immune modulation. Aberrant glycosylation is often cited as a ‘hallmark of cancer’ but is notably absent from both the original hallmarks of cancer and from the next generation of emerging hallmarks. This review discusses how glycosylation is clearly an enabling characteristic that is causally associated with the acquisition of all the hallmark capabilities. Rather than aberrant glycosylation being itself a hallmark of cancer, another perspective is that glycans play a role in every recognised cancer hallmark.
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              Mammalian glycosylation in immunity.

              Glycosylation produces a diverse and abundant repertoire of glycans, which are collectively known as the glycome. Glycans are one of the four fundamental macromolecular components of all cells, and are highly regulated in the immune system. Their diversity reflects their multiple biological functions that encompass ligands for proteinaceous receptors known as lectins. Since the discovery that selectins and their glycan ligands are important for the regulation of leukocyte trafficking, it has been shown that additional features of the vertebrate immune system are also controlled by endogenous cellular glycosylation. This Review focuses on the emerging immunological roles of the mammalian glycome.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                August 2019
                07 June 2019
                07 June 2019
                : 18
                : 2
                : 983-989
                Affiliations
                Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle Upon Tyne NE1 3BZ, UK
                Author notes
                Correspondence to: Dr Jennifer Munkley, Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle Upon Tyne NE1 3BZ, UK, E-mail: jennifer.munkley@ 123456ncl.ac.uk
                Article
                OL-0-0-10458
                10.3892/ol.2019.10458
                6607188
                31423157
                e099d96d-8480-4520-840f-49e07f8e8c55
                Copyright: © Garnham et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 16 April 2019
                : 04 June 2019
                Categories
                Review

                Oncology & Radiotherapy
                glycosylation,glycans,sialylation,st6 β-galactoside α-2,6- sialyltransferase 1,hallmarks of cancer

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