Project/Area Number |
12219202
|
Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
|
Allocation Type | Single-year Grants |
Review Section |
Biological Sciences
|
Research Institution | The University of Tokyo |
Principal Investigator |
TAKENAWA Tadaomi The University of Tokyo, Inst. Med. Sci., Professor, 医科学研究所, 教授 (40101315)
|
Co-Investigator(Kenkyū-buntansha) |
SUETSUGU Shiro The University of Tokyo, Inst Med.Sci.Res., Associate, 医科学研究所, 助手 (70345031)
三木 裕明 東京大学, 医科学研究所, 助教授 (80302602)
深見 希代子 東京大学, 医科学研究所, 助教授 (40181242)
|
Project Period (FY) |
2000 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥222,800,000 (Direct Cost: ¥222,800,000)
Fiscal Year 2004: ¥48,000,000 (Direct Cost: ¥48,000,000)
Fiscal Year 2003: ¥49,000,000 (Direct Cost: ¥49,000,000)
Fiscal Year 2002: ¥46,000,000 (Direct Cost: ¥46,000,000)
Fiscal Year 2001: ¥42,600,000 (Direct Cost: ¥42,600,000)
Fiscal Year 2000: ¥37,200,000 (Direct Cost: ¥37,200,000)
|
Keywords | Actin cytoskeleton / Invasion / Metastasis / WAVE / B16 cells / lamellipodia / 癌細胞 / 細胞運動 / アクチン / WASP / 糸状突起 / 葉状突起 / 系状突起 |
Research Abstract |
We found N-WASP and WAVE which are involved in actin polymerization at leading edge, and induce filopodia and lamellipodia formation. There are 3 types of WAVE. Among them, WAVE2 is ubiquitously expressed in a wide of tissues and plays crucial role in cell movement at leading edge. We next prepared WAVE1 and 2 knock out mice and established mouse embryonic fibroblasts which do not have WAVE1 or WAVE2. WAVE2-deficient MEF did not induce lamellipodia formation in response to chemoatractants, and speed of cell movement was very slow. On the other hand, WAVE1-deficient MEFdidnot induce dorsal ruffles, though lamellipodia formation was still observed. We also examined whether WAVE is involved in invasion of B16/F10 cells that are high metastatic cell lines. WAVE1 knock down did not affect the cell movement in 3 D collagen. In contrast, WAVE2 knock down inhibited cell movement, invasion in collagen gels. B16/F10 cells of WAVE2 knock down was also suppressed in metastasis to lung.
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