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Analysis of mechanisms involved in release from cell-cell adhesion and MMP localization during cohort migration of human colon carcinoma cells

人结肠癌细胞群体迁移过程中细胞粘附释放和 MMP 定位的机制分析

基本信息

批准号：
14570194
负责人：
NABESHIMA Kazuki
金额：
$ 1.73万
依托单位：
Fukuoka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570194/
关键词：
cancer invasion metastasis cell migration HGF SF IQGAP1 cohort migration matrix metalloproteinases (MMP)MMP 細胞接着

项目摘要

1) Mechanisms of a compartmentalized release from cell-cell adhesion during cohort migration of carcinoma cellsOur 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 tissuesImmunohistochemcial 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 sheetsAn 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.

1)癌细胞群迁移过程中细胞-细胞粘附的区室化释放机制我们的结果表明，细胞下部细胞-细胞粘附的局部释放，允许细胞延伸前缘移动，至少部分受到IQGAP 1从胞质溶胶到细胞膜的易位及其与E-钙粘蛋白和连环蛋白的复合物形成的调节，随后从E-钙粘蛋白/连环蛋白复合物中释放α-连环蛋白。Rac 1-DA转染抑制IQGAP 1的易位，从而防止癌细胞的群体迁移。相反，Rac 1-DN转染使IQGAP 1与E-cadherin/catenins形成复合物，导致细胞整体运动增强。2）IQGAP 1在人结直肠癌和卵巢癌组织中的表达采用单特异性抗IQGAP 1抗体的免疫组化研究显示，IQGAP 1是结直肠癌和卵巢癌的一个具有统计学意义的独立预后因子。在两种癌症中。IQGAP 1的弥漫性高表达模式与较高的淋巴结和远端淋巴结相关。3）迁移细胞片层中通过细胞-细胞接触调节MT 1-MMP的前细胞特异性表达用MT 1-MMP KNA探针进行的原位杂交研究表明，迁移细胞片层中MT 1-MMP的前细胞特异性表达在mRNA水平上受到细胞-细胞接触的调节。这种细胞-细胞接触依赖性调节不需要通过与聚合的肌动蛋白丝结合形成紧密的细胞-细胞接触。