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BAG-1 accelerates cell motility of human gastric cancer cells

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Abstract

BAG-1 is a Hsp70/Hsc70-binding protein that interacts with Bcl-2, Raf-1, steroid hormone receptors, Siah-1, and hepatocyte growth factor (HGF) receptors, implying multiple functions for the BAG-1 protein. Here, we provide evidence that gene transfer-mediated overexpression of BAG-1 markedly enhances the motility of human gastric cancer cells. Two independent in vitro migration assays showed that the BAG-1-expressing MKN74 cells exhibited more active migration compared with control transfectants or parent MKN74 cells. In MKN74 cells, the overexpression of BAG-1 affected neither cell adhesion capability nor migration responses to HGF. The promotive effect of BAG-1 on cell migration was similarly observed in transfectants of another human gastric cancer MKN45 cell line. In BAG-1 transfected gastric cancer MKN74 cells, BAG-1 colocalized with cytokeratin as well as actin filaments, and was concentrated at membrane ruffles induced by lysophosphatidic acid (LPA). Taken together, these studies demonstrate that BAG-1 has a novel function as promoter of cell migration in human gastric cancer cells, possibly through cooperation with cytoskeletal proteins.

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Acknowledgements

This work was supported by Grants-in-Aid for Scientific Research on Priority Area-Cancer-from the Ministry of Education, Science, Sports and Culture, and Grants for Cancer Research from the Ministry of Health and Welfare (K Imai and M Adachi), Japan and by National Institutes of Health Grant CA-67329 (JC Reed).

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Authors and Affiliations

  1. First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, 060-8543, Japan

    Yasuyoshi Naishiro, Masaaki Adachi, Hiroyuki Okuda, Atsushi Yawata, Yuji Hinoda & Kohzoh Imai

  2. Department of Pathology, Cancer Research Institute, Sapporo Medical University School of Medicine, Sapporo, 060-8543, Japan

    Toshihiro Mitaka

  3. The Burnham Institute, Cancer Research Center, 10901 N. Torrey Pines Road, La Jolla, 92037, California, USA

    Shinichi Takayama & John C Reed

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  1. Yasuyoshi Naishiro
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  2. Masaaki Adachi
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  3. Hiroyuki Okuda
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  4. Atsushi Yawata
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  5. Toshihiro Mitaka
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  6. Shinichi Takayama
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  7. John C Reed
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  8. Yuji Hinoda
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  9. Kohzoh Imai
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Naishiro, Y., Adachi, M., Okuda, H. et al. BAG-1 accelerates cell motility of human gastric cancer cells. Oncogene 18, 3244–3251 (1999). https://doi.org/10.1038/sj.onc.1202661

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