Abstract
Members of the LAP protein family, LET-413 in Caenorhabditis elegans, Scribble in Drosophila melanogaster and Erbin, Lano, Densin-180 and hScrib in mammals, have conserved structural features. LET-413 and Scribble are junctional proteins involved in establishing and maintaining epithelial cell polarity. scribble also behaves as a neoplastic tumor suppressor gene. We show here that, in epithelial cells, hScrib is recruited at cell–cell junctions in an E-cadherin-dependent manner as shown by calcium switch assays in MDCK cells, re-expression of E-cadherin in MDA-231 cells treated by 5-Aza-2′-deoxycytidine (5Aza) and siRNA experiments. hScrib is restricted at the basolateral membrane of epithelial cells by its LRR domain and is enriched in Triton X-100-insoluble fractions. In breast cancers, most lobular tumors did not express hScrib and E-cadherin while ductal tumors had a less frequent downregulation of hScrib. Our data provide additional insights on the modalities of recruitment of hScrib at the cell–cell junctions and establish a potential link between the E-cadherin and hScrib tumor suppressors.
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Acknowledgements
We are grateful to Dr T Nagase for the KIAA0147 cDNA, Dr R Kemler for E-cadherin-positive and -negative fibroblasts, Dr G Monges for human colon samples and R Galindo for cell sorting expertises. The Laboratory of Molecular Pharmacology is supported by INSERM, Institut Paoli-Calmettes, Ligue Nationale Contre le Cancer (Label Ligue), Fondation de France, Cancéropole PACA and ACI ‘Jeune Chercheur’. CN and SA are recipients of Conseil Régional/Ipsogen fellowships. SN is a recipient of a Ligue Contre le Cancer fellowship.
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Navarro, C., Nola, S., Audebert, S. et al. Junctional recruitment of mammalian Scribble relies on E-cadherin engagement. Oncogene 24, 4330–4339 (2005). https://doi.org/10.1038/sj.onc.1208632
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DOI: https://doi.org/10.1038/sj.onc.1208632
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