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
Externally publishedYes

Fingerprint

Catenins
Neoplasm Metastasis
ErbB-2 Receptor
Tyrosine
Neoplasms
Phosphorylation
Cadherins
Morphogenesis
Cell Adhesion
Stomach Neoplasms
Phenotype
Cell Line

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

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

In: Oncogene, Vol. 13, No. 5, 1996, p. 883-889.

Research output: Contribution to journalArticle

Shibata, Tatsuhiro ; Ochiai, Atsushi ; Kanai, Yae ; Akimoto, Shingo ; Gotoh, Masahiro ; Yasui, Nobutaka ; Machinami, Rikuo ; Hirohashi, Setsuo. / 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. In: Oncogene. 1996 ; Vol. 13, No. 5. pp. 883-889.
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AU - Kanai, Yae

AU - Akimoto, Shingo

AU - Gotoh, Masahiro

AU - Yasui, Nobutaka

AU - Machinami, Rikuo

AU - Hirohashi, Setsuo

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