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Published on: June 9, 2023
ROR2 knockdown suppresses breast cancer growth through PI3K/ATK signaling
Muhong Guo1, Ge Ma2, Xiaolan Zhang3
1Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Abstract:
The receptor tyrosine kinase like orphan receptor 2 (ROR2) has been implicated in the pathogenesis of a variety of human cancers, including breast cancer. Here, we analyzed the clinical significance of ROR2 in breast cancer (BC) progression, and its function in the regulation of BC cell proliferation and growth. Analysis of ROR2 mRNA levels in 45 BC tissues and adjacent non-tumor tissues revealed that ROR2 expression was significantly increased in BC tissues, and that it correlated with tumor diameter. Kaplan-Meier disease-free survival (DFS) analysis demonstrated that BC patients with higher ROR2 expression had lower DFS. Knockdown of ROR2 suppressed in vitro proliferation of BC cells and promoted apoptosis, while ROR2 overexpression induced BC cell proliferation and suppressed apoptosis. Importantly, ROR2 suppression also reduced the tumor growth in mouse BC xenografts, indicating that ROR2 promotes BC tumorigenesis in vivo. In addition, our data revealed that ROR2 promotes proliferation of BC cells by activating the PI3K/AKT signaling pathway. Together, our results indicate that ROR2 acts as an oncogenic gene in breast cancer, and suggest that the ROR2/PI3K/AKT regulatory network contributes to breast cancer progression.
Insights
Receptor tyrosine kinase-like orphan receptor 2 (ROR2) drives breast cancer progression by promoting cell proliferation and reducing survival. Targeting ROR2 may offer a new therapeutic strategy for breast cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is implicated in various cancers.
- Its role in breast cancer (BC) progression requires further elucidation.
Purpose of the Study:
- To investigate the clinical significance of ROR2 in breast cancer (BC) progression.
- To determine the functional role of ROR2 in BC cell proliferation, growth, and tumorigenesis.
Main Methods:
- Analysis of ROR2 mRNA levels in BC tissues and adjacent non-tumor tissues.
- Kaplan-Meier disease-free survival (DFS) analysis.
- In vitro cell proliferation and apoptosis assays.
- In vivo mouse BC xenograft models.
- Investigation of the PI3K/AKT signaling pathway.
Main Results:
- ROR2 expression was significantly elevated in BC tissues and correlated with tumor diameter.
- Higher ROR2 expression was associated with lower DFS in BC patients.
- ROR2 knockdown suppressed BC cell proliferation and induced apoptosis, while ROR2 overexpression had opposite effects.
- ROR2 suppression reduced tumor growth in vivo.
- ROR2 promotes BC cell proliferation by activating the PI3K/AKT pathway.
Conclusions:
- ROR2 functions as an oncogenic gene in breast cancer.
- The ROR2/PI3K/AKT regulatory network is crucial for BC progression.
- ROR2 represents a potential therapeutic target for breast cancer treatment.
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