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

Tatsuhiro Shibata, Atsushi Ochiai, Yae Kanai, Shingo Akimoto, Masahiro Gotoh, Nobutaka Yasui, Rikuo Machinami, Setsuo Hirohashi

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Aberrant tyrosine phosphorylation of β-catenin inactivates the E-cadherin-mediated cell adhesion and invasion suppressor system in cancer cells. Elucidation of the association between β-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 β-catenin, which binds to c-erbB-2 but not to cadherin, inhibited the association between endogenous β-catenin and c-erbB-2 protein, and suppressed the tyrosine phosphorylation of β-catenin. Cells expressing truncated β-catenin exhibited markedly reduced invasiveness in vitro and peritoneal metastasis in vivo, and developed an epithelial morphology. These results suggest that tyrosine phosphorylation of β-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 β-catenin effectively prevents invasion and metastasis of cancer cells.

Original languageEnglish
Pages (from-to)883-889
Number of pages7
JournalOncogene
Volume13
Issue number5
Publication statusPublished - 1996

Keywords

  • Metastasis
  • Protein-protein interaction
  • c-erbB-2
  • β-catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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