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 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 alpha-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 alpha-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.
Takemoto
H
H
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, 2-2-E2, Yamadaoka, Suita, Osaka 565-0871 Japan.
Doki
Y
Y
Shiozaki
H
H
Imamura
H
H
Utsunomiya
T
T
Miyata
H
H
Yano
M
M
Inoue
M
M
Fujiwara
Y
Y
Monden
M
M
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051178:alpha Catenin; D051176:beta Catenin; D020703:ras GTPase-Activating Proteins
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C101203:IQ motif containing GTPase activating protein 1; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D020703:ras GTPase-Activating Proteins