Junctional recruitment of mammalian Scribble relies on E-cadherin engagement

C Navarro, S Nola, S Audebert, MJ Santoni, JP Arsanto… - Oncogene, 2005 - nature.com
C Navarro, S Nola, S Audebert, MJ Santoni, JP Arsanto, C Ginestier, S Marchetto…
Oncogene, 2005nature.com
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 …
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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