Glycans and Cancer

Taniguchi, Naoyuki; Kizuka, Yasuhiko

doi:10.1016/bs.acr.2014.11.001

Cited by 324 publications

(153 citation statements)

References 172 publications

(195 reference statements)

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“…In N-linked glycosylation preassembled blocks of 14 sugars are transferred co-translationally via the amide group of an asparagine residue and are then further processed [21]. Addition of O-GlcNAc (O-GlcNAcylation) occurs almost exclusively within the cell as an alternative to phosphorylation, while N- and O-glycans tend to be found at the cell surface as secreted entities, meaning that intra-cellular proteins may be effected by O-GlcNAcylation while interactions at the cell surface often involve N- glycans and O-glycans [17, 20, 22]. …”

Section: Glycosylationmentioning

confidence: 99%

Hallmarks of glycosylation in cancer

2016

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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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Section: Glycosylationmentioning

confidence: 99%

Hallmarks of glycosylation in cancer

2016

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“…Modifications in glycosyltransferase and/or glycosidase expression, activity, and structure play a key role in the onset and progression of cancer, epithelial-mesenchymal transition (EMT), and metastasis [62-64]. These changes cause concomitant reconfiguration of the “glycocode” of tumor cells through fundamental processes in glycosylation, such as N- and O-glycosylation.…”

Section: Hypoxia Regulates Glycosyltransferases Glycosidases and Nucmentioning

confidence: 99%

“…The N-glycosylation process follows coordinated steps that occur along the endoplasmic reticulum (ER) to Golgi, and its physiological functions include cellular mechanisms involved in cell–cell adhesion, cell motility, signal transduction, and host–pathogen recognition [3, 62, 104]. Changes in the N-glycosylation process can be related to oncogenesis and cancer progression.…”

Section: Hypoxia Changes Membrane Glycoconjugates In Tumor Cellsmentioning

confidence: 99%

“…This endo-β-glucuronidase catalyzes the cleavage of heparan sulfate (HS) side-chains, enhancing tumor cell invasion and migration, and releasing important HS-binding cytokines, relevant to angiogenesis, wound healing, and tumor growth [62]. The transfection of the Hpa gene into poorly metastatic cell lines is associated with a significant increase in metastasis in vivo , and clinical studies have correlated increased Hpa activity with invasion and poor prognosis [89-91].…”

Section: Hypoxia Regulates Glycosyltransferases Glycosidases and Nucmentioning

confidence: 99%

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Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Silva-filho¹,

Sena²,

Lima

et al. 2017

Cell Physiol Biochem

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Post-translational and co-translational enzymatic addition of glycans (glycosylation) to proteins, lipids, and other carbohydrates, is a powerful regulator of the molecular machinery involved in cell cycle, adhesion, invasion, and signal transduction, and is usually seen in both in vivo and in vitro cancer models. Glycosyltransferases can alter the glycosylation pattern of normal cells, subsequently leading to the establishment and progression of several diseases, including cancer. Furthermore, a growing amount of research has shown that different oxygen tensions, mainly hypoxia, leads to a markedly altered glycosylation, resulting in altered glycan-receptor interactions. Alteration of intracellular glucose metabolism, from aerobic cellular respiration to anaerobic glycolysis, inhibition of integrin 3α1β translocation to the plasma membrane, decreased 1,2-fucosylation of cell-surface glycans, and galectin overexpression are some consequences of the hypoxic tumor microenvironment. Additionally, increased expression of gangliosides carrying N-glycolyl sialic acid can also be significantly affected by hypoxia. For all these reasons, it is possible to realize that hypoxia strongly alters glycobiologic events within tumors, leading to changes in their behavior. This review aims to analyze the complexity and importance of glycoconjugates and their molecular interaction network in the hypoxic context of many solid tumors.

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“…Compelling data have shown that core-fucosylation of glycoproteins regulates a wide range of cellular functions. For example, many studies have revealed that increased core fucosylation is often associated with cancer progression 10–12 . AFP-L3, the core-fucosylated α-fetoprotein has been approved by regulatory agency as a biomarker for hepatocellular carcinoma, a major form of liver cancer 13 .…”

Section: Introductionmentioning

confidence: 99%

Designer α1,6-Fucosidase Mutants Enable Direct Core Fucosylation of Intact N-Glycopeptides and N-Glycoproteins

Zhu

Christopher

et al. 2017

J. Am. Chem. Soc.

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Core fucosylation of N-glycoproteins plays a crucial role in modulating the biological functions of glycoproteins. Yet, the synthesis of structurally well-defined, core-fucosylated glycoproteins remains a challenging task due to the complexity in multi-step chemical synthesis or the inability of the biosynthetic α1,6-fucosyltransferase (FUT8) to directly fucosylate full-size mature N-glycans in a chemoenzymatic approach. We report in this paper the design and generation of potential α1,6-fucosynthase and fucoligase for direct core-fucosylation of intact N-glycoproteins. We found that mutation at the nucleophilic residue (D200) did not provide a typical glycosynthase from this bacterial enzyme, but several mutants with mutation at the general acid/base residue E274 of the Lactobacillus casei α1,6-fucosidase, including E274A, E274S, and E274G, acted as efficient glycoligases that could fucosylate a wide variety of complex N-glycopeptides and intact glycoproteins by using α-fucosyl fluoride as a simple donor substrate. Studies on the substrate specificity revealed that the α1,6-fucosidase mutants could introduce an α1,6-fucose moiety specifically at the Asn-linked GlcNAc moiety not only to GlcNAc-peptide, but also to high-mannose and complex type N-glycans in the context of N-glycopeptides, N-glycoproteins, and intact antibodies. This discovery opens a new avenue to a wide variety of homogeneous, core-fucosylated N-glycopeptides and N-glycoproteins that are hitherto difficult to obtain for structural and functional studies.

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Glycans and Cancer

Cited by 324 publications

References 172 publications

Hallmarks of glycosylation in cancer

Hallmarks of glycosylation in cancer

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Designer α1,6-Fucosidase Mutants Enable Direct Core Fucosylation of Intact N-Glycopeptides and N-Glycoproteins

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