ArticleThe Journal of clinical investigation2016
Wnt5a induces ROR1/ROR2 heterooligomerization to enhance leukemia chemotaxis and proliferation.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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Who cites it
129 citing papers in PubMed, 184 citations in OpenAlex.
- Review
- Paediatric Therapeutic Development Workshop on rhabdomyosarcoma.British journal of cancer · 2026Review
- The multifaceted roles of receptor tyrosine pseudokinases in cellular signalling.Biochemical Society transactions · 2026Review
- Conformational cycling of the Wntless transporter drives trafficking and secretion of Wnt morphogens.Nature communications · 2026Article
- Article
- Repurposing of ivacaftor shows potential to treat ROR1 expressing high-grade serous ovarian cancer.Therapeutic advances in medical oncology · 2026Article
- Wnt signaling - using the bloodstream to send a message.Cellular and molecular life sciences : CMLS · 2025Review
- SOX2 utilizes FOXA1 as a heteromeric transcriptional partner to drive proliferation in therapy-resistant prostate cancer.bioRxiv : the preprint server for biology · 2025Article
- Novel Para-Phenylenediamine-Based Derivatives as Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1) Inhibitors: An In Vitro Preliminary Characterization.ChemMedChem · 2025Article
- Wnt5a induces ROR1 dependent NF-κB activation to enhance MMP-9 expression and invasiveness in chronic lymphocytic leukemia.Leukemia · 2025Article
- Uncovering a Novel Role of ROR1 in the Epigenetic Regulation of Tumor Suppressor Gene CREB3L1 in Triple-Negative Breast Cancer Cells.Biomolecules · 2025Article
- Advances in the development of Wnt/β-catenin signaling inhibitors.RSC medicinal chemistry · 2025Review
- Article
- A novel fully human anti-ROR1 antibody PBA-0405 optimized for ADCC, induces potent anti-tumor activity against both solid and hematological malignancies.Frontiers in immunology · 2025Article
- Targeting Wnt-driven metabolic adaptations in cancer: integrating glycolysis, glutaminolysis, IDO1-mediated immune evasion, and therapeutic delivery strategies.Frontiers in cell and developmental biology · 2025Review
- The Multi-Kinase Inhibitor GZD824 (Olverembatinib) Shows Pre-Clinical Efficacy in Endometrial Cancer.Cancer medicine · 2025Article
- Therapeutic advances in the targeting of ROR1 in hematological cancers.Cell death discovery · 2024Review
- DPP an extracellular matrix molecule induces Wnt5a mediated signaling to promote the differentiation of adult stem cells into odontogenic lineage.Scientific reports · 2024Article
- Transcriptomic and proteomic differences in BTK-WT and BTK-mutated CLL and their changes during therapy with pirtobrutinib.Blood advances · 2024Article
- Variant Transcript of ROR1 ENST00000545203 Does Not Encode ROR1 Protein.Biomedicines · 2024Article
69 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution.
Funding
Abstract
Evolutionarily conserved receptor tyrosine kinase–like orphan receptor-1 and -2 (ROR1/2) are considered distinct receptors for Wnt5a and are implicated in noncanonical Wnt signaling in organogenesis and cancer metastasis. We found that Wnt5a enhanced proliferation and migration of chronic lymphocytic leukemia (CLL) cells and that these effects were blocked by the humanized anti-ROR1 mAb cirmtuzumab (UC-961). Treatment of CLL cells with Wnt5a induced ROR1 to oligomerize with ROR2 and recruit guanine exchange factors (GEFs), which activated Rac1 and RhoA; siRNA-mediated silencing of either ROR1 or ROR2 or treatment with UC-961 inhibited these effects. Using the ROR1-deficient CLL cell line MEC1, we demonstrated that ectopic ROR1 expression induced ROR1/ROR2 heterooligomers, which recruited GEFs, and enhanced proliferation, cytokine-directed migration, and engraftment potential of MEC1 cells in immune-deficient mice. Notably, treatment with UC-961 inhibited engraftment of ROR1+ leukemia cells in immune-competent ROR1-transgenic mice. Molecular analysis revealed that the extracellular Kringle domain is required for ROR1/ROR2 heterooligomerization and the cysteine-rich domain or intracellular proline-rich domain is required for Wnt5a-induced recruitment of GEFs to ROR1/ROR2. This study identifies an interaction between ROR1 and ROR2 that is required for Wnt5a signaling that promotes leukemia chemotaxis and proliferation.
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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 OpenQuestion graph.