| Budget Amount *help |
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
In this study, we have investigated the roles of ganglioside GD3 in converging process of the cell signals of proliferation and adhesion in cancer cells by forming molecular complex in the vicinity of cell membrane in GD3+human melanoma cells.
We reported that ganglioside GD3 enhances cell proliferation and invasion of melanomas causing stronger tyrosine-phosphorylation of FAK, p130Cas and paxillin after stimulation with fetal calf serum. Besides signals via growth factor/receptor, adhesion signals via integrin might be also enhanced by GD3. Here, roles of integrin-mediated signaling in the cell proliferation and invasion, and in the activation of adaptor molecules were examined, showing that integrin β1 was also important for the cell growth and invasion. FAK, p130Cas and paxillin underwent stronger tyrosine-phosphorylation in GD3+ cells than in GD3- cells during the adhesion to collagen type I in the absence of serum. Furthermore, molecules activated by GD3 in the vicinity of membranes were searched. Among Src family kinases (SFKs), i.e. Yes, Src and Fyn expressed in the melanoma cell lines, only Yes was involved in the malignant properties such as cell proliferation and invasion.
Consequently, in GD3+ cells, it was demonstrated that integrins are involved in cell growth and invasion, and similar activation of FAK, p130Cas and paxillin during cell adhesion to those detected in FCS-treated cells was observed. These results suggest that ganglioside GD3 is important for converging process of the two major signaling pathways for cell proliferation and adhesion leading to strong activation of FAK, p130Cas and paxillin in the vicinity of cell membrane in GD3+ human melanoma cells.
Now, we are investigating the molecular mechanisms for the triggering of the conversion of the signals for cell proliferation and adhesion by GD3, in the vicinity of cell membrane.
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