| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Outline of Final Research Achievements |
Rho family GTPases are crucial for mechanical force-induced actin cytoskeletal reorganization; however, the mechanism underlying force-induced activation of Rho family GTPases is unknown. A screen of short-hairpin RNAs targeting 63 Rho-guanine nucleotide exchange factors (Rho-GEFs) revealed that at least 11 Rho-GEFs are involved in cyclic-stretch-induced reorientation of vascular endothelial cells. Among 11 Rho-GEFs, Solo is involved in cell-cell-adhesion- and cadherin-mediated mechanical force-induced RhoA activation and reorientation of endothelial cells. We also identified at least 5 Rho-GEFs that are involved in extracellular matrix (ECM) stiffness-induced transformation of MCF-10A human breast epithelial cells cultured in 3D ECM conditions. Among them, Farp1 binds to integrins and plays a critical role in cell adhesion, proliferation, and morphogenesis.
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