Preventing E-cadherin aberrant N -glycosylation at Asn-554 improves its critical function in gastric cancer
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-cadher...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2016
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| In: |
Oncogene
Year: 2015, Jahrgang: 35, Heft: 13, Pages: 1619-1631 |
| ISSN: | 1476-5594 |
| DOI: | 10.1038/onc.2015.225 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/onc.2015.225 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/onc2015225 
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| Verfasserangaben: | S. Carvalho, T.A. Catarino, A.M. Dias, M. Kato, A. Almeida, B. Hessling, J. Figueiredo, F. Gärtner, J.M. Sanches, T. Ruppert, E. Miyoshi, M. Pierce, F. Carneiro, D. Kolarich, R. Seruca, Y. Yamaguchi, N. Taniguchi, C.A. Reis and S.S. Pinho |
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| 100 | 1 | |a Carvalho, Silvia L. |e VerfasserIn |0 (DE-588)1208256459 |0 (DE-627)1694498247 |4 aut | |
| 245 | 1 | 0 | |a Preventing E-cadherin aberrant N -glycosylation at Asn-554 improves its critical function in gastric cancer |c S. Carvalho, T.A. Catarino, A.M. Dias, M. Kato, A. Almeida, B. Hessling, J. Figueiredo, F. Gärtner, J.M. Sanches, T. Ruppert, E. Miyoshi, M. Pierce, F. Carneiro, D. Kolarich, R. Seruca, Y. Yamaguchi, N. Taniguchi, C.A. Reis and S.S. Pinho |
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| 520 | |a 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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| 700 | 1 | |a Dias, A. M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kato, M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Almeida, A. |e VerfasserIn |4 aut | |
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| 700 | 1 | |a Gärtner, F. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sanches, J. M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ruppert, Thorsten |e VerfasserIn |0 (DE-588)142393851 |0 (DE-627)635861887 |0 (DE-576)330488821 |4 aut | |
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| 700 | 1 | |a Pierce, M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Carneiro, F. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kolarich, D. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Seruca, R. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Yamaguchi, Y. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Taniguchi, N. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Reis, C. A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pinho, S. S. |e VerfasserIn |4 aut | |
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