Glycosylation and Cancer: Moving Glycomics to the Forefront

Drake, Richard

doi:10.1016/bs.acr.2014.12.002

Cited by 67 publications

(44 citation statements)

References 36 publications

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“…Aberrant surface glycosylation has emerged as a new hallmark of cancer (Munkley and Elliott 2016) These changes often involve the presence of incomplete or truncated glycan structures, the expression of novel carbohydrate moieties that do not occur on healthy cells, and an increased presence of sialic acid on proteins and glycolipids (Hakomori and Kannagi 1983; Drake 2015) Recent evidence suggests that the presence of certain glycan structures is not just an indicator of cancer progression and metastatic potential of tumor (Pinho and Reis 2015) These glycans are also key mediators of several processes involved in tumor cell proliferation, adhesion, and metastasis (Häuselmann and Borsig 2014; Hakomori and Cummings 2012; Pinho and Reis 2015) Thus, establishing connections between glycan structures and their functions has great potential in developing novel cancer prevention, detection and treatment strategies (Dalziel et al 2014; Fuster and Esko 2005)…”

Section: Introductionmentioning

confidence: 99%

Targeting cancer-specific glycans by cyclic peptide lectinomimics

et al. 2017

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The transformation from normal to malignant phenotype in human cancers is associated with aberrant cell-surface glycosylation. Thus, targeting glycosylation changes in cancer is likely to provide not only better insight into the roles of carbohydrates in biological systems, but also facilitate the development of new molecular probes for bioanalytical and biomedical applications. In the reported study, we have synthesized lectinomimics based on odorranalectin 1; the smallest lectin-like cyclic peptide isolated from the frog Odorrana grahami skin, and assessed the ability of these peptides to bind specific carbohydrates on molecular and cellular levels. In addition, we have shown that the disulfide bond found in 1 can be replaced with a lactam bridge. However, the orientation of the lactam bridge, peptides 2 and 3, influenced cyclic peptide‘s conformation and thus these peptides ability to bind carbohydrates. Naturally occurring 1 and its analog 3 that adopt similar conformation in water bind preferentially L-fucose, and to a lesser degree D-galactose and N-acetyl-D-galactosamine, typically found within the mucin O-glycan core structures. In cell-based assays, peptides 1 and 3 showed a similar binding profile to Aleuria aurantia lectin and these two peptides inhibited the migration of metastatic breast cancer cell lines in a Transwell assay. Altogether, the reported data demonstrate the feasibility of designing lectinomimics based on cyclic peptides.

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Section: Introductionmentioning

confidence: 99%

Targeting cancer-specific glycans by cyclic peptide lectinomimics

et al. 2017

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“…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%

“…They are usually associated with cellular mechanisms involving cell–cell and cell–matrix interactions, immune response, and signal transduction [2, 3]. It is estimated that more than 50% of human proteins have a carbohydrate portion, and that this process represents one of the most important protein post-translational modifications [4, 5].…”

Section: Introductionmentioning

confidence: 99%

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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“…Aberrant glycosylation and altered O‐glycan biosynthesis machinery have been implicated with the progression of several cancers including PDAC . Incomplete O‐glycosylation results in the expression of truncated O‐glycans such as Tn antigen and its sialylated form STn antigen whose expression is highly restricted in normal tissues but is found only on tumour tissues .…”

Section: Discussionmentioning

confidence: 99%

Truncated O‐glycans promote epithelial‐to‐mesenchymal transition and stemness properties of pancreatic cancer cells

Thomas

Sagar

Caffrey

et al. 2019

J Cellular Molecular Medi

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Aberrant expression of Sialyl‐Tn (STn) antigen correlates with poor prognosis and reduced patient survival. We demonstrated that expression of Tn and STn in pancreatic ductal adenocarcinoma (PDAC) is due to hypermethylation of Core 1 synthase specific molecular chaperone (COSMC) and enhanced the malignant properties of PDAC cells with an unknown mechanism. To explore the mechanism, we have genetically deleted COSMC in PDAC cells to express truncated O‐glycans (SimpleCells, SC) which enhanced cell migration and invasion. Since epithelial‐to‐mesenchymal transition (EMT) play a vital role in metastasis, we have analysed the induction of EMT in SC cells. Expressions of the mesenchymal markers were significantly high in SC cells as compared to WT cells. Equally, we found reduced expressions of the epithelial markers in SC cells. Re‐expression of COSMC in SC cells reversed the induction of EMT. In addition to this, we also observed an increased cancer stem cell population in SC cells. Furthermore, orthotopic implantation of T3M4 SC cells into athymic nude mice resulted in significantly larger tumours and reduced animal survival. Altogether, these results suggest that aberrant expression of truncated O‐glycans in PDAC cells enhances the tumour aggressiveness through the induction of EMT and stemness properties.

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Glycosylation and Cancer: Moving Glycomics to the Forefront

Cited by 67 publications

References 36 publications

Targeting cancer-specific glycans by cyclic peptide lectinomimics

Targeting cancer-specific glycans by cyclic peptide lectinomimics

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

Truncated O‐glycans promote epithelial‐to‐mesenchymal transition and stemness properties of pancreatic cancer cells

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