Different glycosylation of cadherins from human bladder non-malignant and cancer cell lines

Przybyło, Małgorzata; Hoja-Łukowicz, Dorota; Lityń́ska, Anna; Laidler, Piotr

doi:10.1186/1475-2867-2-6

Cited by 32 publications

(29 citation statements)

References 31 publications

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“…Our study indicated that the expression of ␤(1,6)-branched oligosaccharides and poly-N-acetyllactosamine on N-cadherin was enhanced after expression of GnT-V. N-Linked ␤(1,6) branching and poly-N-acetyllactosamine have been associated, in some cases, with the increased invasive and metastatic potential of tumor cells (reviewed in Ref. 43); our results were, therefore, consistent with phenotypic changes in some transformed cells (44) and GnT-V-overexpressing cells (5). Moreover, our results also provided direct evidence that poly-N-acetyllactosamine shows concomitant increased expression when N-linked ␤(1,6) branches are increased by GnT-V overexpression.…”

Section: Discussionsupporting

confidence: 86%

N-Acetylglucosaminyltransferase V Expression Levels Regulate Cadherin-associated Homotypic Cell-Cell Adhesion and Intracellular Signaling Pathways

Guo

Lee

Kamar

et al. 2003

Journal of Biological Chemistry

140

131

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A common glycan alteration in transformed cells and human tumors is the highly elevated levels of N-linked ␤(1,6)glycans caused by increased transcription of Nacetylglucosaminyltransferase V (GnT-V). Here, we define the involvement of GnT-V in modulation of homotypic cell-cell adhesion in human fibrosarcoma HT1080 and mouse NIH3T3 cells. Increased GnT-V expression resulted in a significant decrease in the rates of calciumdependent cell-cell adhesion. Reduced cell-cell adhesion was blocked by function-blocking antibody against Ncadherin and abrogated by pre-treatment of cells with swainsonine, demonstrating the involvement of N-cadherin in the cell-cell adhesion and that changes in Nlinked ␤(1,6)glycan expression are responsible for the reduction in rates of adhesion, although this reduction could be mediated by the altered N-linked glycosylation of glycoproteins other than N-cadherin. Overexpression of GnT-V had no effect on the levels of cell surface expression of N-cadherin; however, it did cause a marked enhancement of both ␤(1,6) branching and poly-Nacetyllactosamine expression on N-cadherin. GnT-V overexpression resulted in decreased N-cadherin clustering on the cell surface induced by anti-N-cadherin antibody and affected the outside-in signal transduction pathway of ERK mediated by N-cadherin. Overexpression of GnT-V sensitized stimulation of tyrosine phosphorylation of catenins by growth factors and expression of v-src, which is consistent with its reduction of cell-cell adhesion. In vitro, GnT-V-overexpressing cells showed increased motility concomitant with increased phosphorylation of catenins. Moreover, GnT-V-deficient embryo fibroblasts from GnT-V homozygous null mice (GnT-V ؊/؊ ) express N-cadherin and showed significantly increased levels of N-cadherin-based cell-cell adhesion compared with those from GnT-V ؉/؊ mice. These levels of adhesion were inhibited significantly by transient expression of GnT-V, confirming the hypothesis that levels of GnT-V can regulate cadherin-associated homotypic cell-cell adhesion. Aberrant N-linked ␤(1,6) branching that occurs during oncogenesis can, therefore, lessen cell-cell adhesion, contributing to increased cellular motility and invasiveness.Changes in the expression of many cell surface adhesion receptors, including integrins, cadherins, CD44, and members of the immunoglobulin superfamily such as intercellular adhesion molecule, mediate cell-cell and cell-ECM 1 interactions that are clearly critical as cells undergo oncogenesis and show changes in motility and invasiveness (1-3). Recent studies demonstrate that aberrant glycosylation of several types of cell surface receptors results in dysfunctional intracellular signaling and altered cellular behavior. For example, mutations in an N-acetylglucosaminyltransferase, POMGnT-I, cause aberrant glycosylation of skeletal muscle dystrophin, resulting in dysfunctional neuromuscular junctions (4). Mutations in POMGnT-I have been shown to result in multiple phenotypes, some of which have been classified as "muscle-eye-b...

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Section: Discussionsupporting

confidence: 86%

N-Acetylglucosaminyltransferase V Expression Levels Regulate Cadherin-associated Homotypic Cell-Cell Adhesion and Intracellular Signaling Pathways

Guo

Lee

Kamar

et al. 2003

Journal of Biological Chemistry

140

131

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“…Glycosylation is known to be a cell- and tissue-specific event and the levels and pattern of glycosylation of a specific protein vary accordingly with cell and tissue location 28 (Supplementary Figure S1). N -linked glycosylation does not occur at every potential glycosylation site.…”

Section: Resultsmentioning

confidence: 99%

Preventing E-cadherin aberrant N-glycosylation at Asn-554 improves its critical function in gastric cancer

et al. 2015

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E-cadherin is a central molecule in the process of gastric carcinogenesis and its posttranslational modifications by N-glycosylation have been described to induce a deleterious effect on cell adhesion associated with tumor cell invasion. However, the role that site-specific glycosylation of E-cadherin has in its defective function in gastric cancer cells needs to be determined. Using transgenic mice models and human clinical samples, we demonstrated that N-acetylglucosaminyltransferase V (GnT-V)-mediated glycosylation causes an abnormal pattern of E-cadherin expression in the gastric mucosa. In vitro models further indicated that, among the four potential N-glycosylation sites of E-cadherin, Asn-554 is the key site that is selectively modified with β1,6 GlcNAc-branched N-glycans catalyzed by GnT-V. This aberrant glycan modification on this specific asparagine site of E-cadherin was demonstrated to affect its critical functions in gastric cancer cells by affecting E-cadherin cellular localization, cis-dimer formation, molecular assembly and stability of the adherens junctions and cell–cell aggregation, which was further observed in human gastric carcinomas. Interestingly, manipulating this site-specific glycosylation, by preventing Asn-554 from receiving the deleterious branched structures, either by a mutation or by silencing GnT-V, resulted in a protective effect on E-cadherin, precluding its functional dysregulation and contributing to tumor suppression.

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“…Nevertheless, in spite of the few studies dealing with the expression of T and sialyl-T antigens [17-19] or other types of sialylated structures [20,21] in bladder cancer and there are no published data about the expression of related sialyltransferases.…”

Section: Introductionmentioning

confidence: 99%

ST3Gal.I sialyltransferase relevance in bladder cancer tissues and cell lines

et al. 2009

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BackgroundThe T antigen is a tumor-associated structure whose sialylated form (the sialyl-T antigen) involves the altered expression of sialyltransferases and has been related with worse prognosis. Since little or no information is available on this subject, we investigated the regulation of the sialyltransferases, able to sialylate the T antigen, in bladder cancer progression.MethodsMatched samples of urothelium and tumor tissue, and four bladder cancer cell lines were screened for: ST3Gal.I, ST3Gal.II and ST3Gal.IV mRNA level by real-time PCR. Sialyl-T antigen was detected by dot blot and flow cytometry using peanut lectin. Sialyltransferase activity was measured against the T antigen in the cell lines.ResultsIn nonmuscle-invasive bladder cancers, ST3Gal.I mRNA levels were significantly higher than corresponding urothelium (p < 0.001) and this increase was twice more pronounced in cancers with tendency for recurrence. In muscle-invasive cancers and matching urothelium, ST3Gal.I mRNA levels were as elevated as nonmuscle-invasive cancers. Both non-malignant bladder tumors and corresponding urothelium showed ST3Gal.I mRNA levels lower than all the other specimen groups. A good correlation was observed in bladder cancer cell lines between the ST3Gal.I mRNA level, the ST activity (r = 0.99; p = 0.001) and sialyl-T antigen expression, demonstrating that sialylation of T antigen is attributable to ST3Gal.I. The expression of sialyl-T antigens was found in patients' bladder tumors and urothelium, although without a marked relationship with mRNA level. The two ST3Gal.I transcript variants were also equally expressed, independently of cell phenotype or malignancy.ConclusionST3Gal.I plays the major role in the sialylation of the T antigen in bladder cancer. The overexpression of ST3Gal.I seems to be part of the initial oncogenic transformation of bladder and can be considered when predicting cancer progression and recurrence.

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Different glycosylation of cadherins from human bladder non-malignant and cancer cell lines

Abstract: Background: The aim of the present study was to determine whether stage of invasiveness of bladder cancer cell lines contributes to alterations in glycan pattern of their cadherins.

Cited by 32 publications

References 31 publications

N-Acetylglucosaminyltransferase V Expression Levels Regulate Cadherin-associated Homotypic Cell-Cell Adhesion and Intracellular Signaling Pathways

N-Acetylglucosaminyltransferase V Expression Levels Regulate Cadherin-associated Homotypic Cell-Cell Adhesion and Intracellular Signaling Pathways

Preventing E-cadherin aberrant N-glycosylation at Asn-554 improves its critical function in gastric cancer

ST3Gal.I sialyltransferase relevance in bladder cancer tissues and cell lines

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