RON Mediates Tumor-Promoting Effects in Endometrial Adenocarcinoma.

Qin Yu,Xinxin Xu,Yichen Chen,Libo Zhu,Jianzhang Wang,Gen Zou,Xinmei Zhang,Tiantian Li,Shaojie Ding,Xinyue Guo,Bing Wang

doi:10.1155/2021/2282916

Abstract

Endometrial adenocarcinoma is one of the most prevalent female reproductive tract cancers in the world, and the development of effective treatment is still the main goal of its current research. Epithelial-mesenchymal transition (EMT) plays a significant part in the occurrence and development of epithelial carcinoma, including endometrial adenocarcinoma. Recepteur d'origine nantais (RON) induces EMT and promotes proliferation, migration, and invasion in various epithelial-derived cancers, but its role in endometrial adenocarcinoma is still poorly studied. The purpose of this study is to verify the overexpression of RON in endometrial adenocarcinoma and to explore its specific roles. RON expression in tumor lesions was verified by immunohistochemical staining, HEC-1B cells were used to construct stable cell lines with RON overexpression or knockdown to investigate the effects of RON on the function of endometrial adenocarcinoma cells, and xenotransplantation experiment was carried out in nude mice to explore the effect of RON on the growth of endometrial adenocarcinoma in vivo. This study revealed that RON could promote the proliferation, migration, and invasion of HEC-1B cells and induce EMT, and these effects were regulated through the Smad pathway. RON overexpression could promote growth of endometrial adenocarcinoma cells in nude mice, while its inhibitor BMS777607 could restrict this role. RON played an important role in endometrial adenocarcinoma and had a potential to become a new therapeutic target for endometrial adenocarcinoma.

Highlights

Endometrial carcinoma is a common malignancy of female reproductive tract worldwide, and its incidence is increasing gradually
E-cadherin expression was found to be reduced in endometrial adenocarcinoma tissues [16, 17], suggesting that epithelialmesenchymal transition (EMT) is related in the occurrence and development of endometrial adenocarcinoma, and EMT can be used as an entry point for research
The results showed that the staining intensity of Recepteur d’origine nantais (RON) in endometrial adenocarcinoma group was higher than that of the nonendometrial adenocarcinoma group (Figures 1(a)–1(c))

Summary

Introduction

Endometrial carcinoma is a common malignancy of female reproductive tract worldwide, and its incidence is increasing gradually. Endometrial adenocarcinoma usually has a better prognosis, 13-25% of patients still suffer from recurrence and metastasis [3, 4]. The metastasis and spread of cancer are usually the main cause of poor prognosis [5, 6], in which epithelialmesenchymal transition (EMT) plays a vital role [7, 8]. EMT describes a biological process by which epithelial cells lose their identities and gain power to become spindleshaped mesenchymal cells [9, 10]. EMT is involved in important biological processes such as embryogenesis, wound healing, and tissue regeneration [11, 12]. E-cadherin expression was found to be reduced in endometrial adenocarcinoma tissues [16, 17], suggesting that EMT is related in the occurrence and development of endometrial adenocarcinoma, and EMT can be used as an entry point for research

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Conclusion