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Expression of Human MDGA1 Increases Cell Motility and Cell-Cell Adhesion and Reduces Adhesion to Extracellular Matrix Proteins in MDCK Cells

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Cancer Microenvironment

Abstract

Characterization of the novel human protein MDGA1 (MAM Domain containing Glycosylphosphatidylinositol Anchor-1) has been reported in our laboratory in the past few years. hMDGA1 is a glycoprotein containing 955 aminoacids (137 kDa) attached to the eukaryotic cell membrane by a GPI (Glycosylphosphatidylinositol) anchor and localized specifically into membrane microdomains known as lipid rafts. Moreover, MDGA1 protein contains structural features found in different types of cell adhesion molecules (CAMs) such as the presence of immunoglobulin domains and a MAM domain (Meprin, A5 protein, receptor protein-tyrosine phosphatase μ), suggesting a role of MDGA1 in cell migration and/or adhesion. In order to investigate this aim, stable MDCK cell lines expressing MDGA1 or the truncated proteins IgGPI (lacking the MAM domain) and MAMGPI (lacking Ig domains) were generated. Our results reveal that MDGA1 increases the ability of MDCK cells to migrate, as it contains both Ig and MAM domains which have been implicated in cell motility. In addition, cell adhesion to extracellular matrix proteins, mainly to collagen IV, is reduced by MDGA1 and the IgGPI and MAMGPI truncated proteins. Accordingly, silencing MDGA1 by siRNA revealed a significant increase in adhesion to collagen IV. Furthermore, MDGA1 expression, through the intrinsic properties of the MAM domain, increases cell-cell adhesion independently of the cell monolayer used, suggesting that MDGA1 mediates cell-cell adhesiveness in a heterophilic manner.

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Acknowledgments

We are very grateful to Dr. Carmen Rivas (Departamento de Microbiologia. Facultad de Farmacia. UCM) for continuous scientific support and insightful discussions, to Dr. Jesús Cruces (Departamento de Bioquímica. Facultad de Medicina. UAM) for valuable comments and hepful discussions on MDGA1 and to Dr. Miguel Quintanilla (Instituto de Investigaciones Biomédicas. CSIC.) for kindly providing MDCK cells. We also thank Professor Ian Hart (Barts & The London School of Medicine & Dentistry, London, UK) for his hospitality and assistance in the migration assays. A. Diaz-Lopez was a fellowship of Ministerio de Educación y Ciencia of Spain. This work was supported by grants from Fundación Investigación Médica Mútua Madrileña (FMMA) (Spain); Ministerio de Sanidad y Consumo (FIS PI080033) and Red Temática de Investigación Cooperativa de Centros de Cáncer (RTICC) RD06/0020/0021.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University, 28040, Madrid, Spain

    Antonio Díaz-López, Pilar Iniesta, Alberto Morán, Paloma Ortega, Tamara Fernández-Marcelo, Manuel Benito & Carmen De Juan

  2. Surgery Service, San Carlos Hospital, 28040, Madrid, Spain

    Andrés Sánchez-Pernaute & Antonio J. Torres

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  1. Antonio Díaz-López
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  2. Pilar Iniesta
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  9. Carmen De Juan
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Correspondence to Carmen De Juan.

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Díaz-López, A., Iniesta, P., Morán, A. et al. Expression of Human MDGA1 Increases Cell Motility and Cell-Cell Adhesion and Reduces Adhesion to Extracellular Matrix Proteins in MDCK Cells. Cancer Microenvironment 4, 23–32 (2011). https://doi.org/10.1007/s12307-010-0055-2

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