The role and significance of Wnt5a in regulating epithelial–mesenchymal transition in endometrioid adenocarcinoma

Abstract

Purpose: As a non-classical ligand of Wnt, the abnormal regulation of Wnt5a contributes to the progression of malignant tumors; however, its effects differ depending on tumor type. Here, we evaluated the expression and significance of Wnt5a in endometrioid adenocarci-noma and its relationship with epithelial–mesenchymal transition (EMT)-related proteins. Patients and Methods: Immunohistochemical streptavidin-peroxidase method and reverse transcription polymerase chain reaction (RT-PCR) method were used to analyze the expression and correlation of Wnt5a, and EMT-related protein β-catenin, E-cadherin and enhancer of zeste homolog 2 (EZH2) in endometrial cancer tissues and cell samples of each group. Results: The expression of Wnt5a and E-cadherin decreased in the following order, normal endometrium > atypical hyperplasia endometrium > endometrioid adenocarcinoma. In con-trast, the expression of β-catenin and EZH2 increased gradually. Moreover, Wnt5a expression was associated with the degree of tissue differentiation, International Federation of Gynecology and Obstetrics (FIGO) stage, and lymph node metastasis (all P<0.05). Wnt5a expression was also negatively correlated with β-catenin and EZH2 expression and positively correlated with E-cadherin expression. RT-PCR results further indicated that E-cadherin mRNA expression was upregulated in a Wnt5a-overexpressing Ishikawa cell line compared to cells transfected with an empty vector or negative control cells (P<0.01). Furthermore, the expression of EZH2 and β-catenin mRNA was downregulated in overexpressing cells compared to empty vector and negative control cells (P<0.01). Conclusion: Wnt5a may elicit a suppressive effect on endometrioid adenocarcinoma by inhibiting EMT. This study provides a theoretical basis for the pathological diagnosis and targeted therapy of endometrioid adenocarcinoma and extends our understanding of the Wnt5a signaling pathway.