Localization of IQGAP1 is inversely correlated with intercellular adhesion mediated by E-cadherin in gastric cancers

Down-regulation of E-cadherin function is characteristic of cancer cells and might involve the small C-protein Rho family, including pac I and Cdc42, IQGAP I has been reported to be one of the target proteins of pac I and Cdc42, To elucidate the role of IQGAPI in cancer-cell adhesion, its expression was investigated in 47 cases of human gastric cancer by immunohistochemistry and Western blot upon protein fractionation, especially in comparison with E-cadherin and catenin expression. In the non-cancerous columnar epithelium of the stomach, IQGAPI, as well as E-cadherin/catenin, was expressed at the cell-cell boundary. IQGAP I was frequently observed diffusely in the cytoplasm in intestinal-type tumors (20/22 cases) but was expressed at the cell membrane in diffuse-type tumors (19/25 cases), thus showing significant association with tumor differentiation (p, < 0.01). Interestingly, membranous expression of IQGAP I was inversely correlated with that of E-cadherin ( < 0.05) or alpha -catenin (p < 0.001), These observations were consistent with the Western blot results following protein fractionation. IQGAPI was dominantly expressed in the soluble fraction in differentiated tumors; however, in undifferentiated tumors, it was mostly in the insoluble fraction. In contrast, both E-cadherin and <alpha>-catenin were detected only in the insoluble fraction. Thus, subcellular localization of IQGAP I from the cytoplasm to the cell membrane was correlated with E-cadherin dysfunction and tumor dedifferentiation in gastric carcinogenesis. (C) 2001 Wiley-Liss, Inc.