Altered glycosylation in cancer: A promising target for biomarkers and therapeutics

Thomas, Divya; Rathinavel, Ashok Kumar; Radhakrishnan, Prakash

doi:10.1016/j.bbcan.2020.188464

Cited by 191 publications

(171 citation statements)

References 249 publications

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“…Additionally, glycosylation plays a crucial role in intercellular adhesion and regulates the stability and dynamics of proteins in a subtle way ( 44 ), which is likewise involved in the regulation of human CD2/CD58-mediated cell-cell adhesion by conformational adjustment ( 45 ). Fully glycosylated CD58 is more effective in suppressing the formation of E-rosette than the deglycosylated form, so the maintenance of CD58 glycosylation is essential for the exertion of its functional activity ( 46 ).…”

Section: Structure Of Interface In Cd2-cd58mentioning

confidence: 99%

CD58 Immunobiology at a Glance

et al. 2021

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The glycoprotein CD58, also known as lymphocyte-function antigen 3 (LFA-3), is a costimulatory receptor distributed on a broad range of human tissue cells. Its natural ligand CD2 is primarily expressed on the surface of T/NK cells. The CD2-CD58 interaction is an important component of the immunological synapse (IS) that induces activation and proliferation of T/NK cells and triggers a series of intracellular signaling in T/NK cells and target cells, respectively, in addition to promoting cell adhesion and recognition. Furthermore, a soluble form of CD58 (sCD58) is also present in cellular supernatant in vitro and in local tissues in vivo. The sCD58 is involved in T/NK cell-mediated immune responses as an immunosuppressive factor by affecting CD2-CD58 interaction. Altered accumulation of sCD58 may lead to immunosuppression of T/NK cells in the tumor microenvironment, allowing sCD58 as a novel immunotherapeutic target. Recently, the crucial roles of costimulatory molecule CD58 in immunomodulation seem to be reattracting the interests of investigators. In particular, the CD2-CD58 interaction is involved in the regulation of antiviral responses, inflammatory responses in autoimmune diseases, immune rejection of transplantation, and immune evasion of tumor cells. In this review, we provide a comprehensive summary of CD58 immunobiology.

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Section: Structure Of Interface In Cd2-cd58mentioning

confidence: 99%

CD58 Immunobiology at a Glance

et al. 2021

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“…Glycosylation is increasingly implicated in cancer development and progression (Borzym-Kluczyk et al 2012; Munkley and Elliott 2016; Burchell et al 2018; Reily et al 2019), but the underlying mechanisms driving this relationship necessitate substantial additional exploration (Thomas et al 2020). Specifically, glycosyltransferases have been identified in cancer in various roles and scopes: individual GTs in individual cancer types (Miller et al 2015), individual GTs in multiple cancer types, groups of GTs in individual cancers (Carlini et al 2005; Barthel et al 2008; Gupta et al 2020), and groups of GTs in multiple cancers (Petretti et al 2000; Ashkani and Naidoo 2016).…”

Section: Discussionmentioning

confidence: 99%

Differential expression of glycosyltransferases identified through comprehensive pan-cancer analysis

Vora

Cauley

et al. 2021

Preprint

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Despite accumulating evidence supporting a role for glycosylation in cancer progression and prognosis, the complexity of the human glycome and glycoproteome poses many challenges to understanding glycosylation-related events in cancer. In this study, a multifaceted genomics approach was applied to analyze the impact of differential expression of glycosyltransferases (GTs) in 16 cancers. An enzyme list was compiled and curated from numerous resources to create a consensus set of GTs. Resulting enzymes were analyzed for differential expression in cancer, and findings were integrated with experimental evidence from other analyses, including: similarity of healthy expression patterns across orthologous genes, miRNA expression, automatically-mined literature, curation of known cancer biomarkers, N-glycosylation impact, and survival analysis. The resulting list of GTs comprises 222 human enzymes based on annotations from five databases, 84 of which were differentially expressed in more than five cancers, and 14 of which were observed with the same direction of expression change across all implicated cancers. 25 high-value GT candidates were identified by cross-referencing multimodal analysis results, including PYGM, FUT6 and additional fucosyltransferases, several UDP-glucuronosyltransferases, and others, and are suggested for prioritization in future cancer biomarker studies. Relevant findings are available through OncoMX at https://data.oncomx.org, and the overarching pipeline can be used as a framework for similarly analysis across diverse evidence types in cancer. This work is expected to improve the understanding of glycosylation in cancer by transparently defining the space of glycosyltransferase enzymes and harmonizing variable experimental data to enable improved generation of data-driven cancer biomarker hypotheses.

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“…Abnormal structures of glycans are expressed in cancer that are promising biomarkers and targets for therapy. However, changes in the glycosylation pattern make the tumour cells evade immunosurveillance [2]. In this respect, the role of anti-glycan antibodies (AG Abs) in the mechanisms of anticancer defence remains unclear.…”

Section: Introductionmentioning

confidence: 99%

“…We undertook the follow-up study of gastric and colorectal cancer (CRC) patients and used an enzyme-linked immunosorbent assay (ELISA) with polyacrylamide glycoconjugates (PGs) to monitor the levels of IgG Abs reactive to tumour-associated Thomsen-Friedenreich (TF) and its precursor (Tn), and other glycans to assess the association of the AG Abs level with survival and clinical parameters. The increased attention to these TAGs and respective Abs is due to their expression in ma-lignant tumours; the relation to differentiation, invasiveness, and metastasis; as well as the potential for diagnostics, prognosis, and immunotherapy [2,[5][6][7][8]. The expression of the so-called Thomsen-Friedenreich (TF) on red blood cells after treatment with bacterial neuraminidases was described by Thomsen and specified by Friedenreich [9].…”

Section: Introductionmentioning

confidence: 99%

Prospects and Challenges of the Study of Anti-Glycan Antibodies and Microbiota for the Monitoring of Gastrointestinal Cancer

Smorodin

2021

IJMS

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Over the past decades, a large amount of data has been accumulated in various subfields of glycobiology. However, much clinically relevant data and many tools are still not widely used in medicine. Synthetic glycoconjugates with the known structure of glycans are an accurate tool for the study of glycan-binding proteins. We used polyacrylamide glycoconjugates (PGs) including PGs with tumour-associated glycans (TAGs) in immunoassays to assess the prognostic potential of the serum level of anti-glycan antibodies (AG Abs) in gastrointestinal cancer patients and found an association of AG Abs with survival. The specificity of affinity-isolated AG Abs was investigated using synthetic and natural glycoconjugates. AG Abs showed mainly a low specificity to tumour-associated and tumour-derived mucins; therefore, the protective role of the examined circulating AG Abs against cancer remains a challenge. In this review, our findings are analysed and discussed in the context of the contribution of bacteria to the AG Abs stimulus and cancer progression. Examples of the influence of pathogenic bacteria colonising tumours on cancer progression and patient survival through mechanisms of interaction with tumours and dysregulated immune response are considered. The possibilities and problems of the integrative study of AG Abs and the microbiome using high-performance technologies are discussed.

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Altered glycosylation in cancer: A promising target for biomarkers and therapeutics

Cited by 191 publications

References 249 publications

CD58 Immunobiology at a Glance

CD58 Immunobiology at a Glance

Differential expression of glycosyltransferases identified through comprehensive pan-cancer analysis

Prospects and Challenges of the Study of Anti-Glycan Antibodies and Microbiota for the Monitoring of Gastrointestinal Cancer

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