Junctional recruitment of mammalian Scribble relies on E-cadherin engagement.
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.
Navarro
Christel
C
Marseille Cancer Institute, Molecular Pharmacology, UMR 599 Inserm-Institut Paoli-Calmettes, 27 boulevard Leï Roure 13009 Marseille, France.
Nola
Sébastien
S
Audebert
Stéphane
S
Santoni
Marie-Josée
MJ
Arsanto
Jean-Pierre
JP
Ginestier
Christophe
C
Marchetto
Sylvie
S
Jacquemier
Jocelyne
J
Isnardon
Daniel
D
Le Bivic
André
A
Birnbaum
Daniel
D
Borg
Jean-Paul
JP
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions / Q000235:genetics / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008854:Microscopy, Electron; D011485:Protein Binding; D020449:Repetitive Sequences, Amino Acid; D015534:Trans-Activators / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D051178:alpha Catenin; D051176:beta Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C480591:SCRIB protein, human; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D051178:alpha Catenin; D051176:beta Catenin; D007930:Leucine; D002118:Calcium