ARAP3 inhibits peritoneal dissemination of scirrhous gastric carcinoma cells by regulating cell adhesion and invasion

R. Yagi, M. Tanaka, K. Sasaki, R. Kamata, Y. Nakanishi, Y. Kanai, R. Sakai

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

During the analysis of phosphotyrosine-containing proteins in scirrhous gastric carcinoma cell lines, we observed an unusual expression of Arf-GAP with Rho-GAP domain, ankyrin repeat and PH domain 3 (ARAP3), a multimodular signaling protein that is a substrate of Src family kinases. Unlike other phosphotyrosine proteins, such as CUB domain-containing protein 1 (CDCP1) and Homo sapiens chromosome 9 open reading frame 10/oxidative stress-associated Src activator (C9orf10/Ossa), which are overexpressed and hyperphosphorylated in scirrhous gastric carcinoma cell lines, ARAP3 was underexpressed in cancerous human gastric tissues. In this study, we found that overexpression of ARAP3 in the scirrhous gastric carcinoma cell lines significantly reduced peritoneal dissemination. In vitro studies also showed that ARAP3 regulated cell attachment to the extracellular matrix, as well as invasive activities. These effects were suppressed by mutations in the Rho-GTPase-activating protein (GAP) domain or in the C-terminal two tyrosine residues that are phosphorylated by Src. Thus, the expression and phosphorylation state of ARAP3 may affect the invasiveness of cancer by modulating cell adhesion and motility. Our results suggest that ARAP3 is a unique Src substrate that suppresses peritoneal dissemination of scirrhous gastric carcinoma cells.

Original languageEnglish
Pages (from-to)1413-1421
Number of pages9
JournalOncogene
Volume30
Issue number12
DOIs
Publication statusPublished - 2011 Mar 24
Externally publishedYes

Keywords

  • ARAP3
  • Rho- GAP
  • cell-ECM adhesion
  • invasion
  • scirrhous gastric carcinoma

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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