Ganglioside GD3 induces convergence and synergism of adhesion and hepatocyte growth factor/Met signals in melanomas

Authors

  • Keiko Furukawa,

    Corresponding author
    1. Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai, Japan
    2. Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya, Japan
    • Keiko Furukawa, Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto-cho, Kasugai 487-8501, Japan.

      Tel: 81-568-51-6704; Fax: 81-568-51-6704;

      E-mail: keikofu@isc.chubu.ac.jp

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  • Mariko Kambe,

    1. Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai, Japan
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  • Maiko Miyata,

    1. Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai, Japan
    2. Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya, Japan
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  • Yuki Ohkawa,

    1. Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya, Japan
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  • Orie Tajima,

    1. Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai, Japan
    2. Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya, Japan
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  • Koichi Furukawa

    1. Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Abstract

Ganglioside GD3 is highly expressed in human melanomas and enhances malignant properties of melanomas, such as cell proliferation and invasion activity. In this study, we analyzed the effects of GD3 expression on cell signals triggered by hepatocyte growth factor (HGF)/Met interaction and by adhesion to collagen type I (CL-I). Although stimulation of melanoma N1 cells (GD3+ and GD3−) with either HGF or adhesion to CL-I did not show marked differences in the phosphorylation levels of Akt at Ser473 and Thr308 between two types of cells, simultaneous treatment resulted in definite and markedly increased activation of Akt in GD3+ cells. Similar increases were also shown in Erk1/2 phosphorylation levels with the costimulation in GD3+ cells. When resistance to induced apoptosis by H2O2 was examined, only GD3+ cells treated with both HGF and adhesion to CL-I showed clearly low percentages of dead cells compared with GD3− cells or GD3+ cells treated with either one of the stimulants. Cell growth measured by 5-ethynyl-2‘ deoxyuridine uptake also showed synergistic effects in GD3+ cells. These results suggested that GD3 plays a crucial role in the convergence of multiple signals, leading to the synergistic effects of those signals on malignant properties of melanomas.

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