Cortical stabilization of beta-catenin contributes to NHERF1/EBP50 tumor suppressor function

Oncogene. 2007 Aug 9;26(36):5290-9. doi: 10.1038/sj.onc.1210336. Epub 2007 Feb 26.


Anchorage-independent growth is a hallmark of tumor growth and results from enhanced proliferation and altered cell-cell and cell-matrix interactions. By using gene-deficient mouse embryonic fibroblasts (MEFs), we showed for the first time that NHERF1/EBP50 (Na/H exchanger regulator factor 1/ezrin-radixin-moesin binding phosphoprotein 50), an adapter protein with membrane localization under physiological conditions, inhibits cell motility and is required to suppress anchorage-independent growth. Both NHERF1 PDZ domains are necessary for the tumor suppressor effect. NHERF1 associates directly through the PDZ2 domain with beta-catenin and is required for beta-catenin localization at the cell-cell junctions in MEFs. Mechanistically, the absence of NHERF1 selectively decreased the interaction of beta-catenin with E-cadherin, but not with N-cadherin. The ensuing disorganization of E-cadherin-mediated adherens junctions as well as the observed moderate increase in beta-catenin transcriptional activity contributed most likely to the anchorage-independent growth of NHERF1-deficient MEFs. In vivo, NHERF1 is specifically localized at the apical brush-border membrane in intestinal epithelial cells and is required to maintain a fraction of the cortical beta-catenin at this level. Thus, NHERF1 emerges as a cofactor essential for the integrity of epithelial tissues by maintaining the proper localization and complex assembly of beta-catenin.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Division
  • Cell Line, Transformed
  • DNA Primers
  • Fluorescent Antibody Technique
  • Genes, Tumor Suppressor*
  • Mice
  • Phosphoproteins / physiology*
  • Sodium-Hydrogen Exchangers / physiology*
  • beta Catenin / metabolism
  • beta Catenin / physiology*


  • DNA Primers
  • Phosphoproteins
  • Sodium-Hydrogen Exchangers
  • beta Catenin
  • sodium-hydrogen exchanger regulatory factor