Glycosylation: mechanisms, biological functions and clinical implications

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 5, 2024

Protein post-translational modification (PTM) is a covalent process that occurs in proteins during or after translation through the addition removal of one more functional groups, and has profound effect on protein function. Glycosylation most common PTMs, which polysaccharides are transferred to specific amino acid residues by glycosyltransferases. A growing body evidence suggests glycosylation essential for unfolding various activities organisms, such as playing key role regulation function, cell adhesion immune escape. Aberrant also closely associated with development diseases. Abnormal patterns linked emergence health conditions, including cancer, inflammation, autoimmune disorders, several other However, underlying composition structure glycosylated have not been determined. It imperative fully understand internal differential expression glycosylation, incorporate advanced detection technologies keep knowledge advancing. Investigations clinical applications focused sensitive promising biomarkers, effective small molecule targeted drugs emerging vaccines. These studies provide new area novel therapeutic strategies based glycosylation.

Language: Английский

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Sialic acid blockade inhibits the metastatic spread of prostate cancer to bone

EBioMedicine, Journal Year: 2024, Volume and Issue: 104, P. 105163 - 105163

Published: May 20, 2024

Language: Английский

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Altered glycosylation in cancer: molecular functions and therapeutic potential

Cancer Communications, Journal Year: 2024, Volume and Issue: 44(11), P. 1316 - 1336

Published: Sept. 21, 2024

Abstract Glycosylation, a key mode of protein modification in living organisms, is critical regulating various biological functions by influencing folding, transportation, and localization. Changes glycosylation patterns are significant feature cancer, associated with range pathological activities cancer‐related processes, serve as biomarkers providing new targets for cancer diagnosis treatment. Glycoproteins like human epidermal growth factor receptor 2 (HER2) breast alpha‐fetoprotein (AFP) liver carcinoembryonic antigen (CEA) colon prostate‐specific (PSA) prostate all tumor approved clinical use. Here, we introduce the diversity structures newly discovered substrate—glycosylated RNA (glycoRNA). This article focuses primarily on metastasis, immune evasion, metabolic reprogramming, aberrant ferroptosis responses, cellular senescence to illustrate role cancer. Additionally, summarize applications diagnostics, treatment, multidrug resistance. We envision promising future glycosylation.

Language: Английский

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Sialic acid metabolism-based classification reveals novel metabolic subtypes with distinct characteristics of tumor microenvironment and clinical outcomes in gastric cancer

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 22, 2025

High heterogeneity in gastric cancer (GC) remains a challenge for standard treatments and prognosis prediction. Dysregulation of sialic acid metabolism (SiaM) is recognized as key metabolic hallmark tumor immune evasion metastasis. Herein, we aimed to develop SiaM-based classification GC. SiaM-related genes were obtained from the MsigDB database. Bulk single-cell transcriptional data 956 GC patients acquired GEO, TCGA, MEDLINE databases. Proteomic profiles 20 samples derived our institution. The consensus clustering algorithm was applied identify clusters. model established via LASSO regression evaluated Kaplan‒Meier curve ROC analyses. In vitro vivo experiments conducted explore function ST3GAL1 Three SiaM clusters presented distinct patterns clinicopathological features, transcriptomic alterations, microenvironment landscapes Compared with A B, cluster C elevated activity, higher metastatic potential, more abundant immunosuppressive worse prognosis. Based on differentially expressed between these clusters, risk six (ARHGAP6, ST3GAL1, ADAM28, C7, PLCL1, TTC28) then constructed. exhibited robust performance predicting peritoneal metastasis four independent cohorts. As hub gene model, promoted cell migration invasion vivo. Our study proposed novel that identified three subtypes characteristics clinical outcomes

Language: Английский

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ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) synthesis of Siglec ligands mediates anti-tumour immunity in prostate cancer

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: March 6, 2024

Abstract Immune checkpoint blockade has yet to produce robust anti-cancer responses for prostate cancer. Sialyltransferases have been shown across several solid tumours, including breast, melanoma, colorectal and promote immune suppression by synthesising sialoglycans, which act as ligands Siglec receptors. We report that ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) levels negatively correlate with androgen signalling in tumours. demonstrate ST3Gal1 plays an important role modulating tumour evasion through the synthesises of sialoglycans capacity engage Siglec-7 Siglec-9 immunoreceptors preventing clearance cancer cells. Here, we provide evidence expression Siglec-7/9 their respective These interactions can be modulated enzalutamide may maintain treated conclude activity is critical anti-tumour immunity rationale use glyco-immune targeting therapies advanced

Language: Английский

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Regulation of sialic acid metabolism in cancer

Carbohydrate Research, Journal Year: 2024, Volume and Issue: 539, P. 109123 - 109123

Published: April 22, 2024

Sialic acid, the terminal structure of cell surface glycans, has essential functions in regulating immune response, cell-to-cell communication, and adhesion. More importantly, an increased level sialic termed hypersialylation, emerged as a commonly observed phenotype cancer. Therefore, targeting acid ligands (sialoglycans) their receptors (Siglecs) may provide new therapeutic approach for cancer immunotherapy. We highlight complexity metabolism its involvement malignant transformation within individual subtypes. In this review, we focus on dysregulation sialylation, intricate nature synthesis, clinical perspective. aim to brief insight into mechanism hypersialylation how our understanding these processes can be leveraged development novel therapeutics.

Language: Английский

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Targeting aberrant sialylation and fucosylation in prostate cancer cells using potent metabolic inhibitors

Glycobiology, Journal Year: 2023, Volume and Issue: 33(12), P. 1155 - 1171

Published: Oct. 17, 2023

Abstract Aberrant glycosylation is a hallmark of cancer and not just consequence, but also driver malignant phenotype. In prostate cancer, changes in fucosylated sialylated glycans are common this has important implications for tumor progression, metastasis, immune evasion. Glycans hold huge translational potential new therapies targeting tumor-associated currently being tested clinical trials several types. Inhibitors fucosylation sialylation have been developed show promise treatment, development hampered by safety issues related to systemic adverse effects. Recently, potent metabolic inhibitors were designed that reach higher effective concentrations within the cell, thereby rendering them useful tools study as candidates therapeutic testing. Here, we investigated effects global context progression. We find these effectively shut down synthesis remodel glycome with only minor apparent side on other glycan Our results demonstrate treatment or decreases cell growth downregulates expression genes proteins trajectory disease anticipate our findings will lead broader use explore role pathology may pave way cancer.

Language: Английский

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Novel Click Coupling Chemistry to Explore Glycan Recognition

ACS Central Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Language: Английский

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The Impact of the Mass Analyzer and Tissue Section Thickness on Spatial N-Glycomics with MALDI-MSI

Journal of the American Society for Mass Spectrometry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

We compared matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) spatial N-glycomics data sets from Fourier-transform ion cyclotron resonance (FTICR) and orthogonal accelerated time-of-flight (timsTOF) spectrometers of FFPE preserved human kidney samples. also tested different tissue section thicknesses. In these analyses, we assessed the impact analyzer thickness on N-glycan coverage, sensitivity, histological alignment. Our results indicate negligible differences in coverage between two analyzers, where annotation numbers remained consistent were highly reproducible. The timsTOF-MS analyses demonstrated significant advantages with higher duty cycles better lateral resolution, allowing for finer resolution without compromising signal integrity. Specifically, timsTOF was able to generate detailed MALDI-MS images at 20 μm step size, accurately identifying Hex:5 HexNAc:5 dHex:1 as a tubular-specific marker observable delocalization. Despite minor discrepancies, only three species detected by FTICR not using timsTOF, few false-positive annotations analysis attributed lower resolving power, overall consistency instruments high. Importantly, did affect sensitivity average glycan intensity remaining stable 7 2 sections. These findings demonstrate that thick slices can be effectively used workflows, maintaining while enhancing confidence pathohistological evaluations.

Language: Английский

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Aberrant protein glycosylation in the colon adenoma-cancer sequence: Colorectal cancer mechanisms and clinical implications

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 167853 - 167853

Published: April 1, 2025

Language: Английский

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