Dominant negative inhibition of the association between beta-catenin and c-erbB-2 by N-terminally deleted beta-catenin suppresses the invasion and metastasis of cancer cells

Oncogene. 1996 Sep 5;13(5):883-9.


Aberrant tyrosine phosphorylation of beta-catenin inactivates the E-cadherin-mediated cell adhesion and invasion suppressor system in cancer cells. Elucidation of the association between beta-catenin and c-erbB-2 protein prompted us to investigate whether interference with this interaction can change the invasive phenotype. In a human gastric cancer cell line, TMK-1, N-terminally deleted beta-catenin, which binds to c-erbB-2 but not to cadherin, inhibited the association between endogenous beta-catenin and c-erbB-2 protein, and suppressed the tyrosine phosphorylation of beta-catenin. Cells expressing truncated beta-catenin exhibited markedly reduced invasiveness in vitro and peritoneal metastasis in vivo, and developed an epithelial morphology. These results suggest that tyrosine phosphorylation of beta-catenin regulated by c-erbB-2 protein may play an important role in the invasion, metastasis and morphogenesis of cancer cells and that inhibition of the aberrant tyrosine phosphorylation of beta-catenin effectively prevents invasion and metastasis of cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Metastasis / genetics*
  • Phosphorylation / drug effects
  • Receptor, ErbB-2 / drug effects
  • Receptor, ErbB-2 / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Deletion
  • Signal Transduction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / secondary*
  • Trans-Activators*
  • Transfection
  • Transforming Growth Factor alpha / pharmacology
  • Transplantation, Heterologous
  • Tyrosine / metabolism
  • beta Catenin


  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Cytoskeletal Proteins
  • Recombinant Proteins
  • Trans-Activators
  • Transforming Growth Factor alpha
  • beta Catenin
  • Tyrosine
  • Receptor, ErbB-2