Research Paper Volume 12, Issue 13 pp 13115—13127
ROR2 knockdown suppresses breast cancer growth through PI3K/ATK signaling
- 1 Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- 2 Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
- 3 Department of Breast Surgery, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China
- 4 Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
Received: January 17, 2020 Accepted: May 25, 2020 Published: July 2, 2020
https://doi.org/10.18632/aging.103400How to Cite
Copyright © 2020 Guo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.