Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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Outline of Final Research Achievements |
Pathological observations show that cancer cells invade the surrounding stroma in collective groups rather than through single cell migration. We studied the role of the actin-binding protein Girdin in collective cancer cell migration. We found that Girdin was essential for the collective migration of the skin cancer cell line A431 on collagen gels as well as their invasion in an organotypic culture model. We provide evidence that Girdin binds to β-catenin that plays important roles in E-cadherin-mediated cell-cell adhesion. Girdin-depleted cells displayed scattering and impaired cell-cell adhesion. Girdin depletion led to impaired cytoskeletal association of the β-catenin complex, which was accompanied by changes in the supracellular actin cytoskeletal organization. Finally, we showed the significance of Girdin expression in the progression of human skin cancer. Collectively, our results suggest that Girdin is an important modulator of the collective behavior of cancer cells.
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