Hallmarks of glycosylation in cancer

Munkley, Jennifer; Elliott, David J.

doi:10.18632/oncotarget.8155

Cited by 378 publications

(317 citation statements)

References 153 publications

(168 reference statements)

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“…Mannose, an intermediate metabolite of galactose metabolism pathway, plays an essential role in N-linked glycosylation, which modified certain proteins at the post-translational step. It was reported that high mannose glycans were increased in breast cancer progression 29 and glycans took part in dominant cancer progression phases, such as cancer cell proliferative signaling, activating invasion and metastasis, and tumor promoting inflammation 30 . Our previous study observed that D-Mannose was elevated in late stage esophageal cancer patients 31 , consistent with the finding of higher levels of D-Mannose in PLP and CRC cases compared to controls.…”

Section: Discussionmentioning

confidence: 99%

Global and targeted serum metabolic profiling of colorectal cancer progression

Yin

Sánchez-Espiridión

Lin

et al. 2017

Cancer

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Background Patients with colorectal adenoma polyps (PLP) are at higher risk of developing colorectal cancer (CRC). However, the development of improved and robust biomarkers to enable screening, surveillance and early detection of PLP and CRC continues to be a challenge. The aim of this study was to identify biomarkers of progression to CRC by metabolomic profiling of human serum samples using a multistage approach. Methods Metabolomic profiling was conducted using Metabolon platform for 30 PLP, 30 CRC and 30 control subjects followed by targeted validation of top metabolites in an additional set of 50 CRC, 50 PLP and 50 controls using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Unconditional multivariable logistic regression models adjusted for covariates were used to evaluate association with PLP and CRC risks. Results For the discovery phase, 404 serum metabolites were detected with 50 metabolites showing differential levels between PLP, CRC and controls (P for trend<0.05). Following validation, three top metabolites (xanthine, hypoxanthine and D-mannose) were validated showing lower levels of xanthine and hypoxanthine and higher level of D-mannose in PLP and CRC cases compared to controls. Further exploratory analysis of metabolic pathways revealed key roles for urea cycle and caffeine metabolism associated with PLP and CRC risks. Additionally, joint effect of top metabolites with smoking and significant interaction with BMI were also observed. Analysis of hypoxanthine to xanthine levels as ratio indicated association with CRC progression. Conclusions Our results suggest the potential utility of circulating metabolites as novel biomarkers for early detection of CRC.

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Section: Discussionmentioning

confidence: 99%

Global and targeted serum metabolic profiling of colorectal cancer progression

Yin

Sánchez-Espiridión

Lin

et al. 2017

Cancer

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“…Among modifications in ECM composition, the majority occurs through PGs glycosylation, either enhancing or decreasing the expression of some of these molecules, such as syndecans, or inhibiting the production of others [6, 160-162]. The association between hypoxia and tumor progression is also correlated with alterations in ECM composition through HIF-1α control of the glycosylation process [163-165].…”

Section: Alterations In the Cell–cell And Cell–extracellular Matrix Imentioning

confidence: 99%

“…Aberrant glycosylation has been largely recognized as a hallmark of neoplastic tissue and allows the acquisition of all the hallmarks of cancer [6]. During cancer progression, changes in the glycosylation patterns of cell surface and secreted glycoproteins, leading to tumor proliferation, invasion, epithelial-mesenchymal transition, metastasis, and angiogenesis have been observed [7-10].…”

Section: Introductionmentioning

confidence: 99%

“…During cancer progression, changes in the glycosylation patterns of cell surface and secreted glycoproteins, leading to tumor proliferation, invasion, epithelial-mesenchymal transition, metastasis, and angiogenesis have been observed [7-10]. The crucial role of glycans in a cancer context is also reflected in its use as a biomarker, since most tumor markers approved by the Food and Drug Administration (FDA) are glycoproteins or glycan antigens [6]. …”

Section: Introductionmentioning

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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“…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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Hallmarks of glycosylation in cancer

Cited by 378 publications

References 153 publications

Global and targeted serum metabolic profiling of colorectal cancer progression

Global and targeted serum metabolic profiling of colorectal cancer progression

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

Targeting cancer-specific glycans by cyclic peptide lectinomimics

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