Abstract: Background: Ras homolog gene family member A (RhoA) is involved in Wnt-5a–induced migration of gastric and breast cancer cells. We investigated the roles of RhoA and Wnt-5a in ovarian carcinoma. Methods: RhoA and Wnt-5a mRNA and protein expression in normal fallopian tube epithelium, benign tumors, primary ovarian carcinomas, and metastatic omentum were quantified. RhoA or Wnt-5a was knocked down in OVCAR3 ovarian carcinoma cells using siRNAs and cell phenotype and expression of relevant molecules were assayed. Results: RhoA and Wnt-5a mRNA and protein expression were found to be significantly higher in metastatic omentum than in ovarian carcinomas, benign tumors, and normal fallopian tube epithelium (p < 0.05), and positively associated with differentiation and FIGO staging (stage I/II vs. stage III/IV) in ovarian carcinoma (p < 0.05). RhoA and Wnt-5a expression were positively correlated in ovarian carcinoma (p = 0.001, R2 = 0.1669). RhoA or Wnt-5a knockdown downregulated RhoA and Wnt-5a expression; reduced cell proliferation; promoted G1 arrest and apoptosis; suppressed lamellipodia formation, cell migration, and invasion; and reduced PI3K, Akt, p70S6k, Bcl-xL, survivin, and VEGF mRNA or protein expression. Conclusions: This is the first demonstration that RhoA and Wnt-5a are associated with ovarian carcinogenesis and apoptosis inhibition; there might be positive correlation between RhoA and Wnt-5a expression. RhoA is a potential tumorigenesis, differentiation, and progression biomarker in ovarian carcinoma.
Keywords: ovarian carcinoma; RhoA; Wnt-5a signaling; tumorigenesis and progression; phenotype
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Chen, S.; Wang, J.; Gou, W.-F.; Xiu, Y.-L.; Zheng, H.-C.; Zong, Z.-H.; Takano, Y.; Zhao, Y. The Involvement of RhoA and Wnt-5a in the Tumorigenesis and Progression of Ovarian Epithelial Carcinoma. Int. J. Mol. Sci. 2013, 14, 24187-24199.
Chen S, Wang J, Gou W-F, Xiu Y-L, Zheng H-C, Zong Z-H, Takano Y, Zhao Y. The Involvement of RhoA and Wnt-5a in the Tumorigenesis and Progression of Ovarian Epithelial Carcinoma. International Journal of Molecular Sciences. 2013; 14(12):24187-24199.
Chen, Shuo; Wang, Jun; Gou, Wen-Feng; Xiu, Ying-Ling; Zheng, Hua-Chuan; Zong, Zhi-Hong; Takano, Yasuo; Zhao, Yang. 2013. "The Involvement of RhoA and Wnt-5a in the Tumorigenesis and Progression of Ovarian Epithelial Carcinoma." Int. J. Mol. Sci. 14, no. 12: 24187-24199.