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- Shigeru Hashimoto
- Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan; Laboratory of Molecular Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan; and Laboratory of Molecular Pathogenesis, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
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- Yasuhito Onodera
- Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan; Laboratory of Molecular Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan; and Laboratory of Molecular Pathogenesis, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
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- Ari Hashimoto
- Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan; Laboratory of Molecular Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan; and Laboratory of Molecular Pathogenesis, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
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- Miwa Tanaka
- Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan; Laboratory of Molecular Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan; and Laboratory of Molecular Pathogenesis, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
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- Michinari Hamaguchi
- Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan; Laboratory of Molecular Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan; and Laboratory of Molecular Pathogenesis, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
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- Atsuko Yamada
- Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan; Laboratory of Molecular Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan; and Laboratory of Molecular Pathogenesis, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
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- Hisataka Sabe
- Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan; Laboratory of Molecular Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan; and Laboratory of Molecular Pathogenesis, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
抄録
<jats:p> In most human breast cancer cell lines, there is a direct correlation between their <jats:italic>in vivo</jats:italic> invasive phenotypes and <jats:italic>in vitro</jats:italic> invasion activities. Here, we found that ADP-ribosylation factor 6 (Arf6) is localized at the invadopodia of the cultured breast cancer cells MDA-MB-231, and its suppression by a small-interfering RNA duplex effectively blocks the invasive activities of the cells, such as invadopodia formation, localized matrix degradation and Matrigel transmigration but not the cell-adhesion activity. We also found that the GTP hydrolysis-defective mutant Arf6(Q67L) and the GTP-binding defective mutant Arf6(T27N) both blocked these invasive activities but not cell adhesion, suggesting the necessity of continued activation and cycling of the Arf6 GTPase cycle in invasion. Among the different human breast cancer cell lines that we examined, cell lines with high invasive activities expressed higher amounts of Arf6 protein than those in weakly invasive and noninvasive cell lines, although no notable correlation was found between Arf6 mRNA expression levels and invasive activities. Moreover, Matrigel-transmigration activity of all of these invasive cells was blocked effectively by an Arf6 small-interfering RNA duplex. Hence, Arf6 appears to be an integral component of breast cancer invasive activities, and we propose that Arf6 and the intracellular machinery regulating Arf6 during invasion should be considered as therapeutic targets for the prevention of breast cancer invasion. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 101 (17), 6647-6652, 2004-04-15
Proceedings of the National Academy of Sciences
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詳細情報 詳細情報について
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- CRID
- 1362544420467019776
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- NII論文ID
- 80016768917
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- ISSN
- 10916490
- 00278424
- http://id.crossref.org/issn/00278424
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