Sialyltransferase ST3GAL1 promotes cell migration, invasion, and TGF-β1-induced EMT and confers paclitaxel resistance in ovarian cancer

Cell Death and Disease, Journal Year: 2018, Volume and Issue: 9(11)

Published: Oct. 30, 2018

Sialyltransferases transfer sialic acid to nascent oligosaccharides and are upregulated in cancer. The inhibition of sialyltransferases is emerging as a potential strategy prevent metastasis several cancers, including ovarian ST3GAL1 sialyltransferase that catalyzes the from cytidine monophosphate-sialic galactose-containing substrates associated with cancer progression chemoresistance. However, function uncertain. Herein, we use qRT-PCR, western blotting, immunohistochemistry assess expression tissue cell lines investigate whether it influences resistance paclitaxel vitro mouse xenograft model. We found tissues SKOV-3 OVCAR3 but downregulated A2780 cells. Overexpression cells increases growth, migration, invasion whereas knockdown decreases invasion. Furthermore, overexpression while downregulation vitro, tumorigenicity vivo. Transforming growth factor-β1 can increase induce epithelial-mesenchymal transition (EMT). inhibits EMT expression. Taken together, our findings have identified regulatory mechanism involving may be promising target for overcoming carcinoma.

Language: Английский

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Targeting Selectins and Their Ligands in Cancer

Frontiers in Oncology, Journal Year: 2016, Volume and Issue: 6

Published: April 18, 2016

Aberrant glycosylation is a hallmark of cancer cells with increased evidence pointing to role in tumor progression. In particular, aberrant sialylation glycoproteins and glycolipids have been linked immune cell evasion, drug resistance, invasiveness, vascular dissemination leading metastases. Hypersialylation largely the result overexpression sialyltransferases. Humans differentially express twenty different sialyltransferases tissue-specific manner, each which catalyze attachment sialic acids via glycosidic linkages (2-3; 2-6 or 2-8) underlying glycan chain. One important mechanism whereby contributes an enhanced metastatic phenotype generation selectin ligands. Selectin ligand function requires expression sialyl-Lewis X its structural-isomer A, are synthesized by combined action alpha 1-3-fucosyltransferases, 2-3-sialyltransferases, 1-4-galactosyltranferases, N-acetyl--glucosaminyltransferases. The α2-3-sialyltransferases ST3Gal4 ST3Gal6 critical functional E- P-selectin ligands these risk disease solid tumors poor outcome multiple myeloma. Thus, targeting selectins their as well enzymes involved generation, particular sialyltransferases, could be beneficial many patients. Potential strategies include sialyltransferase inhibition use antagonists, such glycomimetic drugs antibodies. Here, we review ongoing efforts optimize potency selectivity inhibitors, including potential for targeted delivery approaches, evaluate utility now early clinical development.

Language: Английский

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Viewing Siglecs through the lens of tumor immunology

Immunological Reviews, Journal Year: 2017, Volume and Issue: 276(1), P. 178 - 191

Published: March 1, 2017

Summary Many Siglecs function as inhibitory receptors on innate and adaptive immune cells may contribute to the attenuation of responses tumors. Siglec 9 neutrophils 7 NK are prominent examples that can potentially dampen anti‐tumor immunity. CD 169 is a an adhesion molecule facilitator recognition internalization sialic acid decorated apoptotic bodies exosomes derived from It both well facilitation have been best studied in tumor context animal models cancer. Modulators likely be developed investigated clinically cancer over next few years.

Language: Английский

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Synthesis of Human Milk Oligosaccharides: Protein Engineering Strategies for Improved Enzymatic Transglycosylation

Molecules, Journal Year: 2019, Volume and Issue: 24(11), P. 2033 - 2033

Published: May 28, 2019

Human milk oligosaccharides (HMOs) signify a unique group of in breast milk, which is major importance for infant health and development. The functional benefits HMOs create an enormous impetus biosynthetic production use as additives formula other products. HMO molecules can be synthesized chemically, via fermentation, by enzymatic synthesis. This treatise discusses these different techniques, with particular focus on harnessing enzymes controlled synthesis molecules. In order to foster precise high-yield synthesis, several novel protein engineering approaches have been reported, mainly concerning changing glycoside hydrolases catalyze relevant transglycosylations. strategies range from rationally modifying specific catalytic residues, over targeted subsite −1 mutations, transplantations designed peptide sequences near the active site, so-called loop engineering. These proven useful enhanced transglycosylation promote types reactions. rationale modification, acceptor binding site matching, engineering, including changes that may alter spatial arrangement water enzyme region, prove enzyme-catalyzed carbohydrate design general.

Language: Английский

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Tumor-associated carbohydrates and immunomodulatory lectins as targets for cancer immunotherapy

Journal for ImmunoTherapy of Cancer, Journal Year: 2020, Volume and Issue: 8(2), P. e001222 - e001222

Published: Oct. 1, 2020

During oncogenesis, tumor cells present specific carbohydrate chains that are new targets for cancer immunotherapy. Whereas these tumor-associated carbohydrates (TACA) can be targeted with antibodies and vaccination approaches, TACA including sialic acid-containing glycans able to inhibit anticancer immune responses by engagement of receptors on leukocytes. A family immune-modulating acid-binding Siglec have been recently described antitumor activity mediated myeloid cells, natural killer T cells. Other TACA-binding selectins linked progression. Recent studies shown glycan-lectin interactions improve For example, between the checkpoint cell immunoglobulin mucin-domain containing-3 lectin galectin-9 in clinical trials. In addition, an antibody against Siglec-15 is being tested early trial. this review, we summarize previous current efforts target inhibitory binding Siglec-sialoglycan axis.

Language: Английский

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