Last update 21 Mar 2024
ROR2
Tyrosine-protein kinase transmembrane receptor ROR2
Last update 21 Mar 2024
Basic Info
Synonyms BDB, BDB1, Neurotrophic tyrosine kinase, receptor-related 2 + [5] |
Introduction Tyrosine-protein kinase receptor which may be involved in the early formation of the chondrocytes. It seems to be required for cartilage and growth plate development (By similarity). Phosphorylates YWHAB, leading to induction of osteogenesis and bone formation (PubMed:17717073). In contrast, has also been shown to have very little tyrosine kinase activity in vitro. May act as a receptor for wnt ligand WNT5A which may result in the inhibition of WNT3A-mediated signaling (PubMed:25029443). |
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100 Clinical Results associated with ROR2
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100 Translational Medicine associated with ROR2
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09 Feb 2024Molecular cancer research : MCR
ROR2/Wnt5a signaling regulates directional cell migration and early tumor cell invasion in ovarian cancer.
Article
Author: Whitney R Grither ; Breanna Baker ; Vasilios A Morikis ; Ma Xenia G Ilagan ; Katherine C Fuh ; Gregory D Longmore
Adhesion to and clearance of the mesothelial monolayer are key early events in metastatic seeding of ovarian cancer. ROR2 is a receptor tyrosine kinase that interacts with Wnt5a ligand to activate non-canonical Wnt signaling and has been previously shown to be upregulated in ovarian cancer tissue. However, no prior study has evaluated the mechanistic role of ROR2 in ovarian cancer. Through a cellular high throughput genetic screen, we independently identified ROR2 as a driver of ovarian tumor cell adhesion and invasion. ROR2 expression in ovarian tumor cells serves to drive directed cell migration preferentially towards areas of high Wnt5a ligand, such as the mesothelial lined omentum. Additionally, ROR2 promotes ovarian tumor cell adhesion and clearance of a mesothelial monolayer. Depletion of ROR2, in tumor cells, reduces metastatic tumor burden in a syngeneic model of ovarian cancer. These findings support the role of ROR2 in ovarian tumor cells as a critical factor contributing to the early steps of metastasis. Therapeutic targeting of the ROR2/Wnt5a signaling axis could provide a means of improving treatment for patients with advanced ovarian cancer. Implications: This study demonstrates that ROR2 in ovarian cancer cells is important for directed migration to the metastatic niche and provides a potential signaling axis of interest for therapeutic targeting in ovarian cancer.
08 Jan 2024NPJ precision oncology
Cancer associated fibroblasts serve as an ovarian cancer stem cell niche through noncanonical Wnt5a signaling.
Article
Author: Yiming Fang ; Xue Xiao ; Ji Wang ; Subramanyam Dasari ; David Pepin ; Kenneth P Nephew ; Dmitriy Zamarin ; Anirban K Mitra
Frequent relapse and chemoresistance cause poor outcome in ovarian cancer (OC) and cancer stem cells (CSCs) are important contributors. While most studies focus exclusively on CSCs, the role of the microenvironment in providing optimal conditions to maintain their tumor-initiating potential remains poorly understood. Cancer associated fibroblasts (CAFs) are a major constituent of the OC tumor microenvironment and we show that CAFs and CSCs are enriched following chemotherapy in patient tumors. CAFs significantly increase OC cell resistance to carboplatin. Using heterotypic CAF-OC cocultures and in vivo limiting dilution assay, we confirm that the CAFs act by enriching the CSC population. CAFs increase the symmetric division of CSCs as well as the dedifferentiation of bulk OC cells into CSCs. The effect of CAFs is limited to OC cells in their immediate neighborhood, which can be prevented by inhibiting Wnt. Analysis of single cell RNA-seq data from OC patients reveal Wnt5a as the highest expressed Wnt in CAFs and that certain subpopulations of CAFs express higher levels of Wnt5a. Our findings demonstrate that Wnt5a from CAFs activate a noncanonical Wnt signaling pathway involving the ROR2/PKC/CREB1 axis in the neighboring CSCs. While canonical Wnt signaling is found to be predominant in interactions between cancer cells in patients, non-canonical Wnt pathway is activated by the CAF-OC crosstalk. Treatment with a Wnt5a inhibitor sensitizes tumors to carboplatin in vivo. Together, our results demonstrate a novel mechanism of CSC maintenance by signals from the microenvironmental CAFs, which can be targeted to treat OC chemoresistance and relapse.
06 Jan 2024Scientific reports
ROR2 expression predicts human induced pluripotent stem cell differentiation into neural stem/progenitor cells and GABAergic neurons.
Article
Author: Takuya Kuroda ; Satoshi Yasuda ; Satoko Matsuyama ; Takumi Miura ; Rumi Sawada ; Akifumi Matsuyama ; Yumiko Yamamoto ; Masaki Suimye Morioka ; Hideya Kawaji ; Takeya Kasukawa ; Masayoshi Itoh ; Hidenori Akutsu ; Jun Kawai ; Yoji Sato
Despite the development of various in vitro differentiation protocols for the efficient derivation of specific cell types, human induced pluripotent stem cell (hiPSC) lines have varing ability to differentiate into specific lineages. Therefore, surrogate markers for accurately predicting the differentiation propensity of hiPSC lines may facilitate cell-based therapeutic product development and manufacture. We attempted to identify marker genes that could predict the differentiation propensity of hiPSCs into neural stem/progenitor cells (NS/PCs). Using Spearman's rank correlation coefficients, we investigated genes in the undifferentiated state, the expression levels of which were significantly correlated with the neuronal differentiation propensity of several hiPSC lines. Among genes significantly correlated with NS/PC differentiation (P < 0.01), we identified ROR2 as a novel predictive marker. ROR2 expression in hiPSCs was negatively correlated with NS/PC differentiation tendency, regardless of the differentiation method, whereas its knockdown enhanced differentiation. ROR2 regulates NS/PC differentiation, suggesting that ROR2 is functionally essential for NS/PC differentiation. Selecting cell lines with relatively low ROR2 expression facilitated identification of hiPSCs that can differentiate into NS/PCs. Cells with ROR2 knockdown showed increased efficiency of differentiation into forebrain GABAergic neurons compared to controls. These findings suggest that ROR2 is a surrogate marker for selecting hiPSC lines appropriate for NS/PC and GABAergic neuronal differentiations.
19 Mar 2024
Phase 1Phase 2ADCFinancial Statement
20 Dec 2023
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