Glycosylation controls cooperative PECAM-VEGFR2-β3 integrin functions at the endothelial surface for tumor angiogenesis

Imamaki, Rie; Ogawa, Kazuko; Kizuka, Yasuhiko; Komi, Yusuke; Kojima, Soichi; Kotani, Norihiro; Honke, Koichi; Honda, Takashi; Taniguchi, Naoyuki; Kitazume, Shinobu

doi:10.1038/s41388-018-0271-7

Cited by 32 publications

(26 citation statements)

References 52 publications

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“…α2,6-sialylation mediates the homophilic interaction of the platelet endothelial cell adhesion molecule (PECAM). Sialylated PECAM interacted with two other sialylated receptors, VEGFR2 and integrin β3, while the inhibition of sialylation in ST6GAL1 −/− mice prevented PECAM-VEGFR2 interaction on the endothelial surface, inducing endothelial cell apoptosis and inhibiting angiogenesis [83].…”

Section: Sialic Acids Promote Tumor Angiogenesismentioning

confidence: 96%

Biological Functions and Analytical Strategies of Sialic Acids in Tumor

Zhou

Yang

Guan

2020

Cells

119

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Sialic acids, a subset of nine carbon acidic sugars, often exist as the terminal sugars of glycans on either glycoproteins or glycolipids on the cell surface. Sialic acids play important roles in many physiological and pathological processes via carbohydrate-protein interactions, including cell–cell communication, bacterial and viral infections. In particular, hypersialylation in tumors, as well as their roles in tumor growth and metastasis, have been widely described. Recent studies have indicated that the aberrant sialylation is a vital way for tumor cells to escape immune surveillance and keep malignance. In this article, we outline the present state of knowledge on the metabolic pathway of human sialic acids, the function of hypersialylation in tumors, as well as the recent labeling and analytical techniques for sialic acids. It is expected to offer a brief introduction of sialic acid metabolism and provide advanced analytical strategies in sialic acid studies.

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Section: Sialic Acids Promote Tumor Angiogenesismentioning

confidence: 96%

Biological Functions and Analytical Strategies of Sialic Acids in Tumor

Zhou

Yang

Guan

2020

Cells

119

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“…N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) are the two major sialic acids in mammals [3]. Because of their negative electric charge, sialic acids play crucial roles in a variety of cellular functions, e.g., cell-cell interaction, determining conformation of glycoproteins on cell membranes, and masking antigenic determinants on receptor molecules [4][5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Sialidase NEU1 suppresses progression of human bladder cancer cells by inhibiting fibronectin-integrin α5β1 interaction and Akt signaling pathway

et al. 2020

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Background: Sialic acids are widely distributed in animal tissues, and aberrantly expressed in a variety of cancer types. High expression of sialic acid contributes to tumor aggressiveness by promoting cell proliferation, migration, angiogenesis, and metastasis. Sialidases are responsible for removal of sialic acids from glycoproteins and glycolipids. Methods: N-glycomics of bladder cancer cells were detected by MALDI-TOF mass spectrometry. Sialic acid modification in bladder cancer tissue was determined by lectin blot. The down-regulation of NEU1 in bladder cancer cells was determined by high resolution liquid chromatography mass spectrometry (HR LC-MS). The effects of sialidase NEU1 expression on proliferation and apoptosis of human bladder cancer cells were examined by western blot, RT-PCR, confocal imaging and flow cytometry. Moreover, the function of sialic acids on fibronectinintegrin α5β1 interaction were assayed by immunoprecipitation and ELISA. The importance of NEU1 in tumor formation in vivo was performed using BALB/c-nu mice. Expression of NEU1 in primary human bladder cancer tissue samples was estimated using bladder cancer tissue microarray. Results: (1) Downregulation of NEU1 was primarily responsible for aberrant expression of sialic acids in bladder cancer cells. (2) Decreased NEU1 expression was correlated with bladder cancer progression. (3) NEU1 overexpression enhanced apoptosis and reduced proliferation of bladder cancer cells. (4) NEU1 disrupted FNintegrin α5β1 interaction and deactivated the Akt signaling pathway. (5) NEU1 significantly suppressed in vivo tumor formation in BALB/c-nu mice. Conclusions: Our data showed that NEU1 inhibited cancer cell proliferation, induced apoptosis, and suppressed tumor formation both in vitro and in vivo, by disrupting interaction of FN and integrin β1 and inhibiting the Akt signaling pathway. Our observations indicate that NEU1 is an important modulator of the malignant properties of bladder cancer cells, and is a potential therapeutic target for prognosis and treatment of bladder cancer.

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“…When human WM793 primary melanoma cells gain metastatic competence, they show increased levels of sialylated αVβ3 integrins [77]. Cooperation of PECAM-VEGFR2-integrin β3 is significantly reduced when integrin β3 lacks 1,6-sialic acid [78].…”

Section: Integrinsmentioning

confidence: 99%

“…Proteins sialylated by ST6GAL1 are integrin beta 1 [110][111][112][113][114][115] and integrin beta3 [78]. ST6Gal I links SA to integrin β1 in α2-6 mode [116].…”

Section: Enzymes Responsible For the Status Of Adhesion Proteinsmentioning

confidence: 99%

Insight in Adhesion Protein Sialylation and Microgravity Dependent Cell Adhesion—An Omics Network Approach

Bauer

Gombocz²,

Wehland

et al. 2020

IJMS

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The adhesion behavior of human tissue cells changes in vitro, when gravity forces affecting these cells are modified. To understand the mechanisms underlying these changes, proteins involved in cell-cell or cell-extracellular matrix adhesion, their expression, accumulation, localization, and posttranslational modification (PTM) regarding changes during exposure to microgravity were investigated. As the sialylation of adhesion proteins is influencing cell adhesion on Earth in vitro and in vivo, we analyzed the sialylation of cell adhesion molecules detected by omics studies on cells, which change their adhesion behavior when exposed to microgravity. Using a knowledge graph created from experimental omics data and semantic searches across several reference databases, we studied the sialylation of adhesion proteins glycosylated at their extracellular domains with regards to its sensitivity to microgravity. This way, experimental omics data networked with the current knowledge about the binding of sialic acids to cell adhesion proteins, its regulation, and interactions in between those proteins provided insights into the mechanisms behind our experimental findings, suggesting that balancing the sialylation against the de-sialylation of the terminal ends of the adhesion proteins’ glycans influences their binding activity. This sheds light on the transition from two- to three-dimensional growth observed in microgravity, mirroring cell migration and cancer metastasis in vivo.

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Glycosylation controls cooperative PECAM-VEGFR2-β3 integrin functions at the endothelial surface for tumor angiogenesis

Cited by 32 publications

References 52 publications

Biological Functions and Analytical Strategies of Sialic Acids in Tumor

Biological Functions and Analytical Strategies of Sialic Acids in Tumor

Sialidase NEU1 suppresses progression of human bladder cancer cells by inhibiting fibronectin-integrin α5β1 interaction and Akt signaling pathway

Insight in Adhesion Protein Sialylation and Microgravity Dependent Cell Adhesion—An Omics Network Approach

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