| Project/Area Number |
14570194
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Fukuoka University |
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Principal Investigator |
NABESHIMA Kazuki Fukuoka University, School of Medicine, Associate Professor, 医学部, 助教授 (40189189)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | cancer / invasion / metastasis / cell migration / HGF / SF / IQGAP1 cohort migration / matrix metalloproteinases (MMP) / MMP / 細胞接着 |
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| Research Abstract |
1) Mechanisms of a compartmentalized release from cell-cell adhesion during cohort migration of carcinoma cells
Our results have shown that a localized release from cell-cell adhesion in the lower portion of cells, which allows cells to extend leading edges to move, is regulated, at least in part, by translocation of IQGAP1 from cytosol to cell membranes and its complex formation with E-cadherin and catenins there, with a consequent release of alpha-catenin from the E-cadherin/catenin complex. Rac1-DA transfection inhibits the translocation of IQGAP1, and thereby prevents cohort migration of cancer cells. On the contrary, Rac1-DN transfection let IQGAP1 form a complex with E-cadherin/catenins, leading to augmented cell movement en mass.
2) IQGAP1 expression in human colorectal and ovarian carcinoma tissues
Immunohistochemcial studies with monospecific anti-IQGAP1 antibody in colorectal carcinoma and ovarian carcinoma have revealed that IQGAP1 is a statistically significant independent prognostic factor. in both carcinomas. A diffuse high expression pattern of IQGAP1 correlated with higher lymph node and distal metastases.
3) Regulation of front cell-specific expression of MT1-MMP via cell-cell contact in migrating cell sheets
An in situ hybridization study with an MT1-MMP KNA probe has revealed that front cell-specific expression of MT1-MMP in migrating cell sheets is regulated by cell-cell contact ~at the mRNA level. This cell-cell contact-dependent regulation does not need formation of tight cell-cell contact via binding to polymerized actin filaments.
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