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  • Oncogenomics
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Variation in cadherins and catenins expression is linked to both proliferation and transformation of Rhabdomyosarcoma

Oncogene volume 23, pages 2420–2430 (2004)Cite this article

Abstract

Cadherins are a family of transmembrane glycoproteins that mediate Ca2+-dependent homophilic cell–cell adhesion and play a crucial role in cell differentiation. E-cadherin-mediated cell–cell adhesion is lost during the development of most epithelial cancers. This study examines cadherin-dependent adhesion in cell lines derived from rhabdomyosarcoma (RMS), a highly malignant soft-tissue tumor committed to the myogenic lineage, but arrested prior to terminal differentiation. We analysed the expression of cadherins and associated catenins at the mRNA and protein levels as well as their localization in nine RMS-derived cell lines relative to normal myoblasts. We show a decrease in the expression of cadherins and catenins in all RMS-derived cell lines compared to control cells. This decrease in the expression of N- and M-cadherin was confirmed in RMS biopsies. In contrast, R-cadherin is found expressed in RMS, whereas it is normally absent in normal myoblasts. We show that a decrease of R-cadherin expression using RNA interference inhibits cell proliferation of the RD cell line. In addition to their diminished expression, cadherins and catenins do not localize to intercellular contacts in embryonal RMS (ERMS), whereas specific persistent localization is seen in alveolar RMS (ARMS)-derived cell lines. Thus, RMS exhibit defects in the expression of molecules of the cadherin family. Defects in the localization of these adhesion molecules at the sites of cell–cell contact are specifically observed in the ERMS subtype. In addition, our data suggest that R-cadherin is a specific diagnostic marker for RMS and is also an important factor of RMS cell proliferation.

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Acknowledgements

We thank P Fort, A Blangy, P Roux and A Bonnet for fruitful discussions, and J Belet and S Zrioual for assistance. We thank B Hipskind for critically reading the manuscript. We thank K Arden (UCSD, USA), P Houghton (Memphis, USA) and T Triche (Los Angeles, USA) for RMS cell lines and M Takaishi (Japan) for anti-R-cadherin antibody. This work was supported by contracts for the Ligue Nationale contre le Cancer (‘Equipe labelisee’), the Association pour la Recherche contre le Cancer (contrat no. 5668), the Association Francaise contre les myopathies. SC was supported by a fellowship from the ARC.

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  1. Centre de Recherche de Biochimie Macromoléculaire (CRBM), CNRS UPR 1086, 1919 Route de Mende, Montpellier Cedex, 34293, France

    Sophie Charrasse, Franck Comunale & Cécile Gauthier-Rouvière

  2. Laboratoire de Pathologie Moleculaire des Cancers, INSERM U 509, Section de Recherche, Institut Curie, 26 rue d’ULM, Paris, Cedex 05, 75248, France

    Elisabeth Gilbert & Olivier Delattre

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  1. Sophie Charrasse
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Correspondence to Cécile Gauthier-Rouvière.

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Charrasse, S., Comunale, F., Gilbert, E. et al. Variation in cadherins and catenins expression is linked to both proliferation and transformation of Rhabdomyosarcoma. Oncogene 23, 2420–2430 (2004). https://doi.org/10.1038/sj.onc.1207382

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