The Involvement of RhoA and Wnt-5a in the Tumorigenesis and Progression of Ovarian Epithelial Carcinoma

International Journal of Molecular Sciences

Shuo Chen²  Jun Wang³  Wen-Feng Gou⁴  Ying-Ling Xiu²  Hua-Chuan Zheng⁴  Zhi-Hong Zong⁴  Yasuo Takano¹ 

[1] Clinical Cancer Institute, Kanagawa Cancer Center, Yokohama 241-0815, Japan; E-Mail:;Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China; E-Mails:;Department of Gynecology, the General Hospital of Shenyang Military Region, Shenyang 110045, China; E-Mail:;Department of Biochemistry and Molecular Biology, Institute of Pathology and Pathophysiology, College of Basic Medicine, China Medical University, Shenyang 110001, China; E-Mails:

关键词: ovarian carcinoma;    RhoA;    Wnt-5a signaling;    tumorigenesis and progression;    phenotype;   

DOI  :  10.3390/ijms141224187

来源: mdpi

【 摘 要 】

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.

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.

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.

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland