The Role and Significance of Wnt5a in Regulating Epithelial-Mesenchymal Transition in Endometrioid Adenocarcinoma

Ningning Yang; Hongchun Chen; Yuchen Huang; Xuexue Song; Panpan Yang; Shan Zhang; Wentian Yan; Nan Li; Zhenzhong Feng

doi:10.2147/CMAR.S319346

The Role and Significance of Wnt5a in Regulating Epithelial-Mesenchymal Transition in Endometrioid Adenocarcinoma

Cancer Manag Res. 2021 Aug 20:13:6527-6535. doi: 10.2147/CMAR.S319346. eCollection 2021.

Authors

Ningning Yang^{1

2}, Hongchun Chen^{1

2}, Yuchen Huang^{1

2}, Xuexue Song³, Panpan Yang⁴, Shan Zhang⁵, Wentian Yan^{1

2}, Nan Li^{1

2}, Zhenzhong Feng^{1

2}

Affiliations

¹ Department of Pathology, First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, People's Republic of China.
² Department of Pathology, Bengbu Medical College, Bengbu, 233000, People's Republic of China.
³ Department of Pathology, First Affiliated Hospital of University of Science and Technology of China, Hefei, 230000, People's Republic of China.
⁴ Department of Pathology, Second Affiliated Hospital of Anhui Medical University, Hefei, 230000, People's Republic of China.
⁵ Department of Pathology, Second People's Hospital of Hefei, Hefei, 230000, People's Republic of China.

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 adenocarcinoma 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 contrast, 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.

Keywords: Wnt5a; endometrioid adenocarcinoma; epithelial–mesenchymal transition; immunohistochemistry.

Grants and funding

This study was supported by the Natural Science Foundation of Anhui Province (No.1908085MH275); the Key Project of Natural Science Foundation of Bengbu Medical College (BYKF1710); the Joint Science and Technology Project of Bengbu City-Bengbu Medical College (BYLK201812).