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Modulation of E-cadherin function and dysfunction by N-glycosylation

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Abstract

Several mechanisms have been proposed to explain the E-cadherin dysfunction in cancer, including genetic and epigenetic alterations. Nevertheless, a significant number of human carcinomas have been seen that show E-cadherin dysfunction that cannot be explained at the genetic/epigenetic level. A substantial body of evidence has appeared recently that supports the view that other mechanisms operating at the post-translational level may also affect E-cadherin function. The present review addresses molecular aspects related to E-cadherin N-glycosylation and evidence is presented showing that the modification of N-linked glycans on E-cadherin can affect the adhesive function of this adhesion molecule. The role of glycosyltransferases involved in the remodeling of N-glycans on E-cadherin, including N-acetylglucosaminyltransferase III (GnT-III), N-acetylglucosaminyltransferase V (GnT-V), and the α1,6 fucosyltransferase (FUT8) enzyme, is also discussed. Finally, this review discusses an alternative functional regulatory mechanism for E-cadherin operating at the post-translational level, N-glycosylation, that may underlie the E-cadherin dysfunction in some carcinomas.

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Abbreviations

GnT-III:

N-Acetylglucosaminyltransferase III

GnT-V:

N-Acetylglucosaminyltransferase V

FUT8:

α1,6 Fucosyltransferase

GnT-IV:

N-Acetylglucosaminyltransferase IV

EC:

Extracellular domain

AJ:

Adherens-junction

ECM:

Extracellular matrix

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Acknowledgments

We thank Prof. Leonor David for the helpful suggestions regarding the manuscript. We also thank Dr. Masaki Kato of the Systems Glycobiology Research Group, RIKEN, Japan, for the technical support regarding Fig. 2b. This work was supported by grants from the Portuguese Foundation for Science and Technology (FCT), project grants [PTDC/CVT/65537/2006; PIC/IC/82716/2007; PTDC/CVT/111358/2009] and a grant in aid for Scientific Research (A) from MEXT, Japan for financial support. S.S.P. also acknowledges FCT [SFRH/BPD/63094/2009], and the Luso-American Foundation (FLAD). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education, and is partially supported by FCT.

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Authors and Affiliations

  1. Institute of Molecular Pathology and Immunology University of Porto (IPATIMUP), Rua Dr Roberto Frias s/n, 4200-465, Porto, Portugal

    Salomé S. Pinho, Raquel Seruca, Fátima Gärtner & Celso A. Reis

  2. Medical Faculty, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal

    Raquel Seruca & Celso A. Reis

  3. Institute of Biomedical Sciences of Abel Salazar (ICBAS), University of Porto, Largo Prof. Abel Salazar 2, 4099-003, Porto, Portugal

    Fátima Gärtner & Celso A. Reis

  4. Systems Glycobiology Research Group, RIKEN Advanced Science Institute, 2-1 Hirosawa Wako, Saitama, 351-0198, Japan

    Yoshiki Yamaguchi & Naoyuki Taniguchi

  5. Division of Regulatory Glycobiology, Tohoku Pharmaceutical University, Sendai, Miyagi, 981-8558, Japan

    Jianguo Gu

  6. Department of Disease Glycomics (Seikagaku Corporation), The Institute of Scientific and Industrial Research, Osaka University, Mihogaoka 8-1, Ibaraki, Osaka, 567-0047, Japan

    Naoyuki Taniguchi

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  1. Salomé S. Pinho
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  2. Raquel Seruca
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  4. Yoshiki Yamaguchi
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  6. Naoyuki Taniguchi
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  7. Celso A. Reis
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Pinho, S.S., Seruca, R., Gärtner, F. et al. Modulation of E-cadherin function and dysfunction by N-glycosylation. Cell. Mol. Life Sci. 68, 1011–1020 (2011). https://doi.org/10.1007/s00018-010-0595-0

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