Arap3 inhibits peritoneal dissemination of scirrhous gastric carcinoma cells by regulating cell adhesion and invasion

Arap3 inhibits peritoneal dissemination of scirrhous gastric carcinoma cells by regulating cell adhesion and invasion

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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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS


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EGFR. _Traffic_ 9: 2236–2252. Article  CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS The pEGFP-ARAP3 plasmid was a kind gift from Krugmann S (Cambridge,


UK). This work was supported by a Grant-in-Aid for Cancer Research and by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Science and Technology of Japan for


the Third Term Comprehensive 10-Year Strategy for Cancer Control. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Growth Factor Division and National Cancer Center Research Institute, Tsukiji,


Tokyo, Japan R Yagi, M Tanaka, R Kamata & R Sakai * Department of Molecular Medicine and Biochemistry, Akita University, School of Medicine, Hondo, Akita, Japan M Tanaka * Department of


Pharmacology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan K Sasaki * Pathology Division, National Cancer Center Research Institute, Tsukiji, Tokyo,


Japan Y Nakanishi & Y Kanai Authors * R Yagi View author publications You can also search for this author inPubMed Google Scholar * M Tanaka View author publications You can also search


for this author inPubMed Google Scholar * K Sasaki View author publications You can also search for this author inPubMed Google Scholar * R Kamata View author publications You can also


search for this author inPubMed Google Scholar * Y Nakanishi View author publications You can also search for this author inPubMed Google Scholar * Y Kanai View author publications You can


also search for this author inPubMed Google Scholar * R Sakai View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to R


Sakai. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. ADDITIONAL INFORMATION Supplementary Information accompanies the paper on the Oncogene website


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ABOUT THIS ARTICLE CITE THIS ARTICLE Yagi, R., Tanaka, M., Sasaki, K. _et al._ ARAP3 inhibits peritoneal dissemination of scirrhous gastric carcinoma cells by regulating cell adhesion and


invasion. _Oncogene_ 30, 1413–1421 (2011). https://doi.org/10.1038/onc.2010.522 Download citation * Received: 01 June 2010 * Revised: 10 September 2010 * Accepted: 07 October 2010 *


Published: 15 November 2010 * Issue Date: 24 March 2011 * DOI: https://doi.org/10.1038/onc.2010.522 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this


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KEYWORDS * ARAP3 * scirrhous gastric carcinoma * Rho-GAP * cell-ECM adhesion * invasion