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

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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.