1. Ectopic repression of receptor tyrosine kinase–like orphan receptor 2 inhibits malignant transformation of ovarian cancer cells by reversing epithelial–mesenchymal transition
- Author
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Ying Xu, Hongluan Mao, Yanhui Ma, Yingxin Pang, Zhe Zhao, Peishu Liu, and Jingjing Lu
- Subjects
0301 basic medicine ,endocrine system ,Epithelial-Mesenchymal Transition ,endocrine system diseases ,Carcinogenesis ,Receptor tyrosine kinase-like orphan receptor ,Biology ,Receptor Tyrosine Kinase-like Orphan Receptors ,Wnt-5a Protein ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Ovarian carcinoma ,Cell Line, Tumor ,medicine ,Humans ,Tyrosine ,Receptor ,RC254-282 ,Aged ,Cell Proliferation ,Orphan receptor ,Ovarian Neoplasms ,Wnt signaling pathway ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,General Medicine ,Middle Aged ,medicine.disease ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,030220 oncology & carcinogenesis ,ROR1 ,Cancer research ,Female ,Ovarian cancer - Abstract
Receptor tyrosine kinase–like orphan receptor 2 is an enzyme-linked receptor which specifically modulates WNT5A signaling and plays an important role in tumorigenesis, invasion, and metastasis; however, the precise role of receptor tyrosine kinase–like orphan receptor 2 in cancer is controversial. The purpose of this study was to investigate the expression and role of receptor tyrosine kinase–like orphan receptor 2 in ovarian carcinoma and clarify the biological functions and interactions of receptor tyrosine kinase–like orphan receptor 2 with non-canonical Wnt pathways in ovarian cancer. The result of the human ovary tissue microarray revealed that the receptor tyrosine kinase–like orphan receptor 2–positive rate increased in malignant epithelial ovarian cancers and was extremely higher in the metastatic tumor tissues, which was also higher than that in the malignant ovarian tumor tissues. In addition, high expression of receptor tyrosine kinase–like orphan receptor 2 was closely related with ovarian cancer grading. The expression of receptor tyrosine kinase–like orphan receptor 2 protein was higher in SKOV3 and A2780 cells than OVCAR3 and 3AO cells. Knockdown of receptor tyrosine kinase–like orphan receptor 2 inhibited ovarian cancer cell proliferation, migration, invasion, and induced morphologic as well as digestive state alterations in stably transfected SKOV3 cells. Detailed study further revealed that silencing of receptor tyrosine kinase–like orphan receptor 2 reversed the epithelial–mesenchymal transition and inhibited non-canonical Wnt signaling. Our findings suggest that receptor tyrosine kinase–like orphan receptor 2 may be an important regulator of epithelial–mesenchymal transition, primarily regulated the non-canonical Wnt signaling pathway in ovarian cancer cells, and may display a promising therapeutic target for ovarian cancer.
- Published
- 2017