ArticleLeukemia2020
The WNT receptor ROR2 drives the interaction of multiple myeloma cells with the microenvironment through AKT activation.
Article in Leukemia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- KDM6A loss enhances oxidative phosphorylation uncovering tissue-level convergent evolution.The EMBO journal · 2026Article
- ROR2-specific CAR T cells are effective against hematologic and solid tumors and well tolerated in mice.Cell reports. Medicine · 2025Article
- Modeling the Bone Marrow Niche in Multiple Myeloma: From 2D Cultures to 3D Systems.International journal of molecular sciences · 2025Review
- Detection of early relapse in multiple myeloma patients.Cell division · 2025Article
- Therapeutic advances in the targeting of ROR1 in hematological cancers.Cell death discovery · 2024Review
- Exploring the promise of regulator of G Protein Signaling 20: insights into potential mechanisms and prospects across solid cancers and hematological malignancies.Cancer cell international · 2024Review
- miR-124-3p and miR-194-5p regulation of the PI3K/AKT pathway via ROR2 in medulloblastoma progression.Cancer gene therapy · 2024Article
- Overexpression of Wnt5a promoted the protective effect of mesenchymal stem cells on Lipopolysaccharide-induced endothelial cell injury via activating PI3K/AKT signaling pathway.BMC infectious diseases · 2024Article
- ROR2 promotes invasion and chemoresistance of triple-negative breast cancer cells by activating PI3K/AKT/mTOR signaling.Oncology research · 2024Article
- Transcription ofGenes · 2023Article
- The Roles of Secreted Wnt Ligands in Cancer.International journal of molecular sciences · 2023Review
- Article
- Wnt pathway in bone: knowledge structure and hot spots from 1993 to 2022.Frontiers in physiology · 2023Article
- Protocol for generation of 3D bone marrow surrogate microenvironments in a rotary cell culture system.STAR protocols · 2022Article
- New insights into the molecular mechanisms of ROR1, ROR2, and PTK7 signaling from the proteomics and pharmacological modulation of ROR1 interactome.Cellular and molecular life sciences : CMLS · 2022Article
- Pathogenic signaling in multiple myeloma.Seminars in oncology · 2022Article
- ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation.Journal of biomedical science · 2021Article
- Prognostic Significance of ROR2 Expression in Patients with Urothelial Carcinoma.Biomedicines · 2021Article
- Review
- Review
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
Abstract
Multiple myeloma is the second most frequent hematological cancer after lymphoma and remains an incurable disease. The pervasive support provided by the bone marrow microenvironment to myeloma cells is crucial for their survival. Here, an unbiased assessment of receptor tyrosine kinases overexpressed in myeloma identified ROR2, a receptor for the WNT noncanonical pathway, as highly expressed in myeloma cells. Its ligand, WNT5A is the most abundant growth factor in the bone marrow of myeloma patients. ROR2 mediates myeloma cells interactions with the surrounding bone marrow and its depletion resulted in detachment of myeloma cells from their niche in an in vivo model, triggering apoptosis and thus markedly delaying disease progression. Using in vitro and ex vivo 3D-culture systems, ROR2 was shown to exert a pivotal role in the adhesion of cancer cells to the microenvironment. Genomic studies revealed that the pathways mostly deregulated by ROR2 overexpression were PI3K/AKT and mTOR. Treatment of cells with specific PI3K inhibitors already used in the clinic reduced myeloma cell adhesion to the bone marrow. Together, our findings support the view that ROR2 and its downstream targets represent a novel therapeutic strategy for the large subgroup of MM patients whose cancer cells show ROR2 overexpression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.