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ROR2 Is Epigenetically Regulated in Endometrial Cancer
Dongli Liu1, Luis Enriquez1, Caroline E Ford1
1Gynaecological Cancer Research Group, Lowy Cancer Research Centre, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
Cancers
|January 26, 2021
Summary
The Wnt signaling receptor ROR2 acts as a tumor suppressor in endometrial cancer (EC). Epigenetic silencing via promoter methylation correlates with reduced ROR2 expression and poorer outcomes, suggesting ROR2 as a potential diagnostic and therapeutic target for EC.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- The Wnt signaling receptor ROR2 is implicated in various cancers, but its specific role in endometrial cancer (EC) is not fully understood.
- Understanding ROR2's function is crucial for identifying potential therapeutic strategies in EC.
Purpose of the Study:
- To investigate the role of ROR2 in endometrial cancer (EC).
- To elucidate the mechanism behind altered ROR2 expression in EC.
- To assess ROR2 as a potential diagnostic or therapeutic candidate for EC.
Main Methods:
- Analysis of ROR2 mRNA expression and clinicopathological parameters in TCGA-UCEC and GEO datasets.
- Assessment of ROR2 promoter methylation in EC cell lines and clinical samples using COBRA and BGS.
- Functional studies involving ROR2 overexpression in EC cell lines to evaluate effects on invasion and epithelial-mesenchymal transition (EMT) markers.
Main Results:
- Reduced ROR2 expression and promoter methylation correlated with shorter overall survival (OS), higher grade, and serous subtype in EC cohorts.
- ROR2 was epigenetically silenced by promoter methylation in both EC patient samples and cell lines.
- ROR2 restoration in EC cells significantly reduced invasion and altered EMT markers, indicating a tumor-suppressive role.
Conclusions:
- ROR2 functions as a tumor suppressor in endometrial cancer.
- Epigenetic silencing of ROR2 via promoter methylation is associated with EC progression.
- ROR2 represents a promising diagnostic and therapeutic target for endometrial cancer.
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