| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Research Abstract |
We have shown that membrane-type 1 matrix metalloproteinase (MT1-MMP) regulate fibronectin (FN) assembly by cleaving it, which results in promotion of cell motility and proliferation. FN matrix assembly requires the increased cytoskeletal tension generated by cadherin adhesions. In a co-culture of Rat1 fibroblasts and MT1-MMP-silenced but not control HT1080 cells, FN fibrils extended from Rat1 to cell-matrix adhesions in HT1080 cells, and N-cadherin adhesions were formed between these cells. MT1-MMP knockdown promoted FN matrix assembly and N-cadherin adhesions in HT1080 cells, which was abrogated by double knockdown with either integrin beta1 or FN. Conversely, inhibition of N-cadherin adhesions suppressed FN matrix formation in MT1-MMP-silenced cells. These data demonstrate that FN assembly initiated by MT1-MMP knockdown results in increased N-cadherin adhesions, which are prerequisite for further FN matrix formation.
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