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      Hallmarks of glycosylation in cancer

      review-article
      1 , 1
      Oncotarget
      Impact Journals LLC
      cancer, glycosylation, hallmarks, glycans, aberrant

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          Abstract

          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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          Most cited references117

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          On the origin of cancer cells.

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            Cancer. p53, guardian of the genome.

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              Genes that mediate breast cancer metastasis to the brain.

              The molecular basis for breast cancer metastasis to the brain is largely unknown. Brain relapse typically occurs years after the removal of a breast tumour, suggesting that disseminated cancer cells must acquire specialized functions to take over this organ. Here we show that breast cancer metastasis to the brain involves mediators of extravasation through non-fenestrated capillaries, complemented by specific enhancers of blood-brain barrier crossing and brain colonization. We isolated cells that preferentially infiltrate the brain from patients with advanced disease. Gene expression analysis of these cells and of clinical samples, coupled with functional analysis, identified the cyclooxygenase COX2 (also known as PTGS2), the epidermal growth factor receptor (EGFR) ligand HBEGF, and the alpha2,6-sialyltransferase ST6GALNAC5 as mediators of cancer cell passage through the blood-brain barrier. EGFR ligands and COX2 were previously linked to breast cancer infiltration of the lungs, but not the bones or liver, suggesting a sharing of these mediators in cerebral and pulmonary metastases. In contrast, ST6GALNAC5 specifically mediates brain metastasis. Normally restricted to the brain, the expression of ST6GALNAC5 in breast cancer cells enhances their adhesion to brain endothelial cells and their passage through the blood-brain barrier. This co-option of a brain sialyltransferase highlights the role of cell-surface glycosylation in organ-specific metastatic interactions.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                7 June 2016
                17 March 2016
                : 7
                : 23
                : 35478-35489
                Affiliations
                1 Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, NE1 3BZ, UK
                Author notes
                Correspondence to: Jennifer Munkley, jennifer.munkley@ 123456ncl.ac.uk
                Article
                8155
                10.18632/oncotarget.8155
                5085245
                27007155
                17311a85-07b7-434d-a956-c8a0b2ba5ac2
                Copyright: © 2016 Munkley and Elliott

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 28 January 2016
                : 2 March 2016
                Categories
                Review

                Oncology & Radiotherapy
                cancer,glycosylation,hallmarks,glycans,aberrant
                Oncology & Radiotherapy
                cancer, glycosylation, hallmarks, glycans, aberrant

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