Premium
Localization of IQGAP1 is inversely correlated with intercellular adhesion mediated by e‐cadherin in gastric cancers
Author(s) -
Takemoto Hiroyoshi,
Doki Yuichiro,
Shiozaki Hitoshi,
Imamura Hiroshi,
Utsunomiya Takehiro,
Miyata Hiroshi,
Yano Masahiko,
Inoue Masatoshi,
Fujiwara Yoshiyuki,
Monden Morito
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(200002)9999:9999<::aid-ijc1121>3.0.co;2-z
Subject(s) - iqgap1 , cadherin , intracellular , adhesion , biology , cancer research , pathology , chemistry , medicine , microbiology and biotechnology , cell , genetics , signal transduction , scaffold protein , organic chemistry
Down‐regulation of E‐cadherin function is characteristic of cancer cells and might involve the small G‐protein Rho family, including Rac1 and Cdc42. IQGAP1 has been reported to be one of the target proteins of Rac1 and Cdc42. To elucidate the role of IQGAP1 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, IQGAP1, as well as E‐cadherin/catenin, was expressed at the cell–cell boundary. IQGAP1 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 IQGAP1 was inversely correlated with that of E‐cadherin ( p < 0.05) or α‐catenin ( p < 0.001). These observations were consistent with the Western blot results following protein fractionation. IQGAP1 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 α‐catenin were detected only in the insoluble fraction. Thus, subcellular localization of IQGAP1 from the cytoplasm to the cell membrane was correlated with E‐cadherin dysfunction and tumor dedifferentiation in gastric carcinogenesis. © 2001 Wiley‐Liss, Inc.