Recent advances in the development of sialyltransferase inhibitors to control cancer metastasis: A comprehensive review

Saoud, Ranim Al; Hamrouni, Amar M; Idris, Adi; Mousa, Walaa K.; Izneid, Tareq Abu

doi:10.1016/j.biopha.2023.115091

Cited by 13 publications

(5 citation statements)

References 176 publications

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“…AAL, GNL, PSA and WFL yielded no difference at all. Comparing the absolute signal response at the end of a dissociation phase and analytical sensitivity between the carcinoma and control exosomes using SNA and MAAII lectins (both sialic acid-specific), the carcinoma exosomes yielded higher parameters and, hence (due to the fact that the same exosome concentration was used for the experiments), are more likely to contain higher amounts of surface sialic acid-containing epitopes, which, again, is in good correlation with the literature data (Figure 4) [40][41][42]. Consistent results could also be obtained for multi-cycle kinetics (MCK) analysis.…”

Section: Lectin-based In-situ Glycoprofilingsupporting

confidence: 86%

Negative Charge-Carrying Glycans Attached to Exosomes as Novel Liquid Biopsy Marker

Kosutova,

Lorencova,

Hires

et al. 2024

Sensors

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Prostate cancer (PCa) is the second most common cancer. In this paper, the isolation and properties of exosomes as potential novel liquid biopsy markers for early PCa liquid biopsy diagnosis are investigated using two prostate human cell lines, i.e., benign (control) cell line RWPE1 and carcinoma cell line 22Rv1. Exosomes produced by both cell lines are characterised by various methods including nanoparticle-tracking analysis, dynamic light scattering, scanning electron microscopy and atomic force microscopy. In addition, surface plasmon resonance (SPR) is used to study three different receptors on the exosomal surface (CD63, CD81 and prostate-specific membrane antigen-PMSA), implementing monoclonal antibodies and identifying the type of glycans present on the surface of exosomes using lectins (glycan-recognising proteins). Electrochemical analysis is used to understand the interfacial properties of exosomes. The results indicate that cancerous exosomes are smaller, are produced at higher concentrations, and exhibit more nega tive zeta potential than the control exosomes. The SPR experiments confirm that negatively charged α-2,3- and α-2,6-sialic acid-containing glycans are found in greater abundance on carcinoma exosomes, whereas bisecting and branched glycans are more abundant in the control exosomes. The SPR results also show that a sandwich antibody/exosomes/lectins configuration could be constructed for effective glycoprofiling of exosomes as a novel liquid biopsy marker.

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Section: Lectin-based In-situ Glycoprofilingsupporting

confidence: 86%

Negative Charge-Carrying Glycans Attached to Exosomes as Novel Liquid Biopsy Marker

Kosutova,

Lorencova,

Hires

et al. 2024

Sensors

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“…Sialic acid fosters tumorigenesis, supporting evasion from apoptosis, facilitating metastasis formation, and fortifying resistance to therapy [ 3 ]. The overexpression of STs, the enzymes responsible for sialic acid addition, intensifies tumor metastasis by bolstering immune evasion, promoting invasion and migration, and diminishing chemotherapy efficacy [ 6 , 10 , 21 ]. Conversely, hyposialylation (decreased sialic acid levels on cell surfaces) also contributes to metastatic spread and chemotherapy evasion in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

“…STs, which are expressed differently in cancer cells, are linked to the growth, invasion, and spread of tumors [3][4][5][6]. Therefore, targeting the aberrant sialylation process, including enzymes in sialic acid biosynthesis, is a potential cancer treatment strategy [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Bioinformatic Analysis of Gene Expression Related to Sialic Acid Biosynthesis in Patients With Medulloblastoma

Bakhit,

Fujii

2024

Cureus

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BackgroundSialic acid, a critical component for cell membrane integrity, undergoes complex biosynthesis involving enzymes like sialyltransferases (STs), impacting cancer progression. Aberrant sialylation by STs is implicated in cancer growth, invasion, and therapy resistance. Medulloblastoma (MB), a pediatric brain tumor with distinct subgroups and variable genetic alterations, poses uncertainty regarding the implications of sialylation. MethodologyThis study employs bioinformatic analyses on bulk and single-cell RNA-sequenced samples to explore atypical gene expressions linked to sialic acid metabolism in MB. A list of sialic biosynthesis-related genes was compiled using the STRING database. Data of MB samples from bulk and single-cell RNA sequencing were obtained from open-source repositories and were differentially analyzed, focusing on molecular subgroups (WNT, SHH, Group 3, and Group 4). The study employed survival analyses, specifically Cox regression, to analyze the overall survival (OS) data obtained through bulk RNA sequencing. ResultsThirty-eight genes/proteins related to sialic acid metabolism were identified. Differential expression analysis between WNT and Group 3 and WNT and Group 4 revealed significant differences in seven and eleven genes, respectively, with consistent ST6GAL2 expression disparities (false discovery rate [FDR] Pvalue < 0.01, log2FC > 0.58). Elevated ST6GAL2 expression correlated with improved OS, with mortality risk reductions ranging from 26% to 48% (P-value < 0.006, Bonferroni-corrected threshold). ConclusionsElevated ST6GAL2 expression correlated with improved OS in diverse MB sample subsets, suggesting potential mechanisms in inhibiting tumor progression and enhancing immune response, requiring experimental validation.

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“…Indeed, we found negligible expression of polySia in skin fibroblasts at basal condition ( Figure 1 A,B). In addition, sialyltransferase inhibitors are compounds that specifically block sialylation with no other expected cellular effects [ 36 ]. Of note, similarly to our experimental design, the study of Sasaki et al [ 53 ] did not include a treatment with the sialyltransferase inhibitor alone for experiments on fibroblasts treated with TGFβ1.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, aberrant sialylation is increasingly recognized as a hallmark of numerous challenging chronic diseases other than cancers, such as autoimmune diseases [ 34 , 35 ]. Of note, potential therapeutic effects of modulating sialyltransferase activity with different compounds were demonstrated both in vitro and in vivo [ 31 , 36 , 37 , 38 ]. As far as the implication of sialylation in skin fibrosis is concerned, a recent study reported that polySia is dysregulated in systemic sclerosis, a multisystem autoimmune disease characterized by fibrosis not only of the skin but also of various internal organs [ 39 ].…”

Section: Introductionmentioning

confidence: 99%

Blockade of Sialylation with Decrease in Polysialic Acid Levels Counteracts Transforming Growth Factor β1-Induced Skin Fibroblast-to-Myofibroblast Transition

Fioretto,

Rosa,

Tani

et al. 2024

Cells

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Aberrant sialylation with overexpression of the homopolymeric glycan polysialic acid (polySia) was recently reported in fibroblasts from fibrotic skin lesions. Yet, whether such a rise in polySia levels or sialylation in general may be functionally implicated in profibrotic activation of fibroblasts and their transition to myofibroblasts remains unknown. Therefore, we herein explored whether inhibition of sialylation could interfere with the process of skin fibroblast-to-myofibroblast transition induced by the master profibrotic mediator transforming growth factor β1 (TGFβ1). Adult human skin fibroblasts were pretreated with the competitive pan-sialyltransferase inhibitor 3-Fax-peracetyl-Neu5Ac (3-Fax) before stimulation with recombinant human TGFβ1, and then analyzed for polySia expression, cell viability, proliferation, migratory ability, and acquisition of myofibroblast-like morphofunctional features. Skin fibroblast stimulation with TGFβ1 resulted in overexpression of polySia, which was effectively blunted by 3-Fax pre-administration. Pretreatment with 3-Fax efficiently lessened TGFβ1-induced skin fibroblast proliferation, migration, changes in cell morphology, and phenotypic and functional differentiation into myofibroblasts, as testified by a significant reduction in FAP, ACTA2, COL1A1, COL1A2, and FN1 gene expression, and α-smooth muscle actin, N-cadherin, COL1A1, and FN-EDA protein levels, as well as a reduced contractile capability. Moreover, skin fibroblasts pre-administered with 3-Fax displayed a significant decrease in Smad3-dependent canonical TGFβ1 signaling. Collectively, our in vitro findings demonstrate for the first time that aberrant sialylation with increased polySia levels has a functional role in skin fibroblast-to-myofibroblast transition and suggest that competitive sialyltransferase inhibition might offer new therapeutic opportunities against skin fibrosis.

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Recent advances in the development of sialyltransferase inhibitors to control cancer metastasis: A comprehensive review

Cited by 13 publications

References 176 publications

Negative Charge-Carrying Glycans Attached to Exosomes as Novel Liquid Biopsy Marker

Negative Charge-Carrying Glycans Attached to Exosomes as Novel Liquid Biopsy Marker

Bioinformatic Analysis of Gene Expression Related to Sialic Acid Biosynthesis in Patients With Medulloblastoma

Blockade of Sialylation with Decrease in Polysialic Acid Levels Counteracts Transforming Growth Factor β1-Induced Skin Fibroblast-to-Myofibroblast Transition

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