Junctional recruitment of mammalian Scribble relies on E-cadherin engagement

Oncogene. 2005 Jun 23;24(27):4330-9. doi: 10.1038/sj.onc.1208632.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Calcium / pharmacology
  • Cell Line
  • Cell Membrane / metabolism
  • Colon / cytology
  • Colon / metabolism
  • Cytoskeletal Proteins / metabolism
  • Dogs
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Humans
  • Intercellular Junctions / genetics
  • Intercellular Junctions / metabolism*
  • Leucine / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microscopy, Electron
  • Protein Binding
  • Repetitive Sequences, Amino Acid
  • Trans-Activators / metabolism
  • Tumor Suppressor Proteins
  • alpha Catenin
  • beta Catenin


  • CTNNA1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • Membrane Proteins
  • SCRIB protein, human
  • Trans-Activators
  • Tumor Suppressor Proteins
  • alpha Catenin
  • beta Catenin
  • Leucine
  • Calcium