Expression of seven main Rho family members in gastric carcinoma

Pan, Yanglin; Bi, Feng; Liu, Na; Xue, Yan; Yao, Xuebiao; Zheng, Yi; Fan, Daiming

doi:10.1016/j.bbrc.2004.01.108

Cited by 161 publications

(132 citation statements)

References 28 publications

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“…1). These results are consistent with those of previous studies [25,26] and suggest that RhoA is involved in the progression of gastric cancers, acting as an oncogene. When the gastric cancers were stratified by differentiation, we found no significant difference in RhoA overexpression between intestinal-type and diffuse-type gastric cancers, indicating that RhoA contributes to the tumorigenesis of both types of gastric cancers.…”

Section: Discussionsupporting

confidence: 93%

Gastrokine 1 inhibits gastric cancer cell migration and invasion by downregulating RhoA expression

et al. 2016

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Background We investigated whether GKN1, a gastric tumor suppressor, contributes to the progression of gastric cancer by regulating RhoA expression. Methods We analyzed the expression of GKN1, RhoA, miR-185, and miR-34a in 35 gastric cancer tissues, and compared their expression with T category and TNM stage. Cell migration and invasion, as well as the expression of epithelial-to-mesenchymal transition (EMT)-related proteins, were assessed in GKN1-and RhoA small interfering RNA (siRhoA)-transfected and recombinant-GKN1-treated AGS and MKN1 gastric cancer cells. Results Expression of RhoA protein and messenger RNA (mRNA) was increased in 15 (42.9 %) and 17 (48.6 %) of 35 gastric cancer tissues respectively, and was associated with higher T category and TNM stage. GKN1 expression was significantly decreased in 27 gastric cancers (77.1 %) with a higher T category, and was inversely correlated with RhoA mRNA expression. In AGS and MKN1 cells, GKN1 expression increased miR-185 and miR-34a expression and reduced RhoA mRNA and protein expression. A positive relationship between GKN1 and miR-34a and miR-185 expression and an inverse relationship between miR-34a and RhoA expression were observed in gastric cancer tissues. Cell migration and invasiveness were markedly decreased in GKN1-and siRhoA-transfected cells. GKN1 expression and silencing of RhoA decreased the expression of the proteins Snail, Slug, and vimentin. Furthermore, miR-185 and miR-34a silencing in MKN1 cells transfected with GKN1 stimulated cell migration and invasion, and increased the expression of EMT-related proteins. Conclusion Our data suggest that GKN1 may inhibit gastric cancer cell migration and invasion by downregulating RhoA expression in a miR-185-and miR-34a-dependent manner.

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Section: Discussionsupporting

confidence: 93%

Gastrokine 1 inhibits gastric cancer cell migration and invasion by downregulating RhoA expression

et al. 2016

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“…Recent findings indicate that Rac1 may play an important role in the carcinogenesis and progression of gastric carcinoma, because increased Rac1 expression was related to higher TNM stages. 22 Genetic deletion of Rac1 has revealed its critical role in cell survival regulation 23 suggesting that increased expression of Rac1 in tumors may protect cells from apoptosis and lead to an increase of cellmatrix-interaction and cell spread. However, despite these important functions that are attributed to Rac1, no association of expression of Rac1 with prognosis was found in our study of gastric carcinomas.…”

Section: The Rho Gtpase Rac1mentioning

confidence: 99%

Combined analysis of Rac1, IQGAP1, Tiam1 and E-cadherin expression in gastric cancer

et al. 2008

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Rho GTPases are a family of major regulators of E-cadherin-mediated cell adhesion that are implicated in the carcinogenic process by deregulated expression of the family members itself or of upstream modulators or downstream effectors. Combined investigation of the Rho GTPase Rac1, the effector protein IQGAP1 and the activator Tiam1 in relation to expression or mutation of E-cadherin in gastric adenocarcinomas has not been reported. The aim of the study was to determine the expression and prognostic significance of Rac1, IQGAP1, Tiam1 and E-cadherin in gastric adenocarcinomas. Gastric carcinomas of 76 patients were investigated immunohistochemically in a tissue microarray study for expression of Rac1, IQGAP1, Tiam1 and E-cadherin. Correlations with clinical and follow-up data were examined. Moderate or strong reactivity for Rac1 was observed in 46% and for Tiam1 in 56% of tumors. Expression of IQGAP1 was present in 59% and of E-cadherin in 87% of tumors. While Rac1 and E-cadherin expression were not related to prognosis, a trend was observed between a lack of IQGAP1 expression (log-rank 0.088) as well as presence of Tiam1 (log-rank 0.097) and favorable prognosis in Kaplan-Meier survival analysis. Expression of Rac1 was positively linked to IQGAP1 expression (P ¼ 0.007, r ¼ 0.343) and tended to be inversely associated with expression of E-cadherin (P ¼ 0.055, r ¼ À0.245). In conclusion, we observed deregulated expression of Rac1, IQGAP1, Tiam1 and E-cadherin in gastric cancer. We present evidence that either upregulation (for Rac1 and IQGAP1) or downregulation (for Tiam1 and E-cadherin) occurs. Rac1 and E-cadherin expression were not related to prognosis, while trends pointing to favorable prognosis of patients with Tiam1 expression and a lack of IQGAP1 expression were observed. These results indicate that the investigated regulators of E-cadherin-mediated cell adhesion play a role in gastric carcinogenesis.

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“…Recently, it has been reported that abnormal expression of these proteins may play a fundamentally important role in the molecular mechanisms involved in carcinogenesis (5,6). Specifically, increased activity and͞or expression of the closely related genes RhoA and RhoC were found in human neoplasms and were further correlated with the degree of malignancy (7)(8)(9)(10)(11)(12)(13). As reported by Clark et al (10), overexpression of RhoC enhanced metastasis of mouse melanoma, whereas expression of the dominant-negative Rho variant inhibited metastasis.…”

mentioning

confidence: 99%

Rho overexpression leads to mitosis-associated detachment of cells from epithelial sheets: A link to the mechanism of cancer dissemination

Vasiliev

Omelchenko

Gelfand

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Dissemination of neoplastic cells from the primary tumor (invasion and metastasis) is a fundamentally dangerous step in multistage carcinogenesis. Recent evidence suggests that Rho GTPase-mediated signaling is linked to dissemination of cells from several different types of human tumors. The Rho family of proteins is typically associated with the regulation of cytoskeletal activity, including actin assembly, microtubule dynamics, and myosin IIdependent contractility of the actin-rich cortex. We examined the effect of overexpression of constitutively active RhoA on islands and monolayers of epithelial cells. Although newly plated cells initially formed small spread islands, there was also a significant population of cells that detached from the substrate, floated in the medium, and then could reattach to the substrate to form new colonies. Detachment of cells from transfected epithelial islands or monolayers occurred in correlation to the plane of cytokinesis after misorientation of the mitotic spindle axis. We suggest that these alterations result from Rho-induced increase of contractility of the cortex of dividing cells, which, during cytokinesis, produces a cell that has budded out of an existing layer of cells. Cell divisionmediated detachment of cells from tissue structures may be an important mechanism of tumor dissemination and metastasis. mitotic spindle ͉ metastasis ͉ contractility T he Rho family of small GTPases, Rho, Rac, and Cdc42, plays essential roles in regulating diverse cellular functions, in particular those associated with cytoskeletal dynamics (1-4). Recently, it has been reported that abnormal expression of these proteins may play a fundamentally important role in the molecular mechanisms involved in carcinogenesis (5, 6). Specifically, increased activity and͞or expression of the closely related genes RhoA and RhoC were found in human neoplasms and were further correlated with the degree of malignancy (7-13). As reported by Clark et al. (10), overexpression of RhoC enhanced metastasis of mouse melanoma, whereas expression of the dominant-negative Rho variant inhibited metastasis. The mechanism that links Rho activity to the ability of cells within a tumor to spread remains a matter of speculation, since Rho activity potentially impinges on multiple signaling pathways.To investigate the mechanisms that might link Rho signaling with tumor proliferation, an IAR-2 epithelial cell line expressing constitutively active RhoA was produced by stable transfection with an enhanced GFP (EGFP)-RhoA Q63L plasmid (4, 14). Overexpression of constitutively active RhoA protein produced dramatic changes in cultures of epithelial cells, including overall cell contraction, mass detachment of cells from the monolayer, multilayering of cells creating cell stacking, and subsequent reattachment of stacked cells to the substrate forming new colonies. Detachment of cells is correlated with cell division and is related to improper orientation of the mitotic spindle, which leads to an altered plane for cytokinesis. We p...

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Expression of seven main Rho family members in gastric carcinoma

Cited by 161 publications

References 28 publications

Gastrokine 1 inhibits gastric cancer cell migration and invasion by downregulating RhoA expression

Gastrokine 1 inhibits gastric cancer cell migration and invasion by downregulating RhoA expression

Combined analysis of Rac1, IQGAP1, Tiam1 and E-cadherin expression in gastric cancer

Rho overexpression leads to mitosis-associated detachment of cells from epithelial sheets: A link to the mechanism of cancer dissemination

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