Affinage

ROR1

Inactive tyrosine-protein kinase transmembrane receptor ROR1 · UniProt Q01973

Length
937 aa
Mass
104.3 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ROR1 is a cell-surface receptor tyrosine kinase-like molecule that drives proliferation, migration, and pro-survival signaling in cancer and tissue regeneration, primarily as a non-canonical Wnt5a receptor (PMID:26690702, PMID:29678828). Although it adopts a kinase fold, ROR1 is a pseudokinase devoid of intrinsic catalytic activity and is instead transphosphorylated by partner kinases such as Met in oncogene-amplified cells (PMID:21487037). Upon Wnt5a stimulation, ROR1 hetero-oligomerizes with ROR2 through its extracellular Kringle domain and recruits guanine nucleotide exchange factors via its cytoplasmic proline-rich domain (PRD), with the single residue P808 being essential for DOCK2 binding and the downstream activation of Rac1/RhoA GTPases and ERK1/2 that promote chemotaxis and proliferation (PMID:26690702, PMID:29678828, PMID:33097837). ROR1 converges on AKT survival signaling through multiple routes: it complexes with casein kinase 1ε to activate PI3K-AKT-CREB (PMID:22403610), cooperates with TCL1 to accelerate leukemogenesis (PMID:24379361), and acts as a kinase-independent scaffold that stabilizes caveolin-1 and CAVIN proteins to maintain caveolae and sustain pro-survival AKT output from EGFR, MET, and IGF-IR (PMID:26725982, PMID:30894682). ROR1 can also directly phosphorylate HER3 at Tyr1307 to engage the LLGL2-MAYA-NSUN6/MST1-YAP axis driving breast cancer bone metastasis (PMID:28114269), and it promotes epithelial-mesenchymal transition through regulation of SNAIL, vimentin, and E-cadherin (PMID:23771907). ROR1 itself is regulated at multiple levels: N-linked glycosylation is required for cell-surface trafficking of the mature receptor (PMID:21481194), HSP90α binds a specific ELHHPNIV motif to protect ROR1 from ubiquitin-proteasome degradation (PMID:33370472, PMID:31726100), and its transcription is induced by Wnt/β-catenin, STAT3, Notch/HIF-1α, and inflammatory NF-κB inputs across diverse tissues (PMID:28790171, PMID:37096681, PMID:37343369, PMID:36314076). Beyond cancer, ROR1 is required for satellite cell proliferation during skeletal muscle regeneration downstream of TNF-α/IL-1β-NF-κB signaling (PMID:28790171).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2011 High

    Established that ROR1 is catalytically inactive, reframing it from an autonomous kinase to a pseudokinase dependent on partner kinases for phosphorylation events.

    Evidence In vitro kinase assays and Met-inhibitor/RNAi experiments in Met-amplified cancer cell lines with in vivo tumorigenesis

    PMID:21487037

    Open questions at the time
    • Whether transphosphorylation by Met is required in non-Met-amplified contexts
    • Functional consequence of the phosphorylated state on downstream signaling not defined
  2. 2011 Medium

    Showed that ROR1 surface display depends on post-translational maturation, linking glycosylation to its functional localization and cytoskeletal effects.

    Evidence N-glycosidase treatment, glycosylation inhibitors, ubiquitination assays, and surface flow cytometry

    PMID:21481194

    Open questions at the time
    • Glycosylation sites not mapped
    • Functional role of mono-ubiquitination unresolved
  3. 2012 Medium

    Connected ROR1 to PI3K-AKT survival signaling by identifying CK1ε as a partner amplifying Wnt5a-driven growth, providing an early mechanistic link to a major oncogenic pathway.

    Evidence Reciprocal Co-IP, siRNA silencing, and in vitro/in vivo breast cancer growth assays

    PMID:22403610

    Open questions at the time
    • Direct CK1ε-ROR1 phosphorylation relationship not established
    • Mechanism connecting CK1ε to PI3K activation undefined
  4. 2013 High

    Demonstrated genetically that ROR1 cooperates with TCL1 to enhance AKT signaling and accelerate leukemia, moving beyond correlation to in vivo epistasis.

    Evidence Co-IP/MS identification of the ROR1-TCL1 complex and ROR1×TCL1 double-transgenic mice with adoptive transfer

    PMID:24379361

    Open questions at the time
    • Direct biochemical mechanism by which TCL1 binding enhances AKT phosphorylation unclear
    • Whether the interaction is direct or bridged not resolved
  5. 2016 High

    Defined the core non-canonical Wnt5a signaling architecture by mapping the domains required for ROR1/ROR2 hetero-oligomerization and GEF-driven Rac1/RhoA activation.

    Evidence Domain-deletion/truncation constructs, Co-IP, GTPase activation assays, and in vivo engraftment in CLL

    PMID:26690702

    Open questions at the time
    • Identity of the GEFs not specified at this stage
    • Stoichiometry of the ROR1/ROR2 oligomer unknown
  6. 2016 High

    Revealed a kinase-independent scaffolding role for ROR1 in stabilizing caveolin-1 and maintaining caveolae, broadening its function beyond Wnt signaling to multi-RTK survival.

    Evidence Co-IP, kinase-dead mutants, EM/IF of caveolae, and AKT signaling assays in lung cancer with EGFR-TKI resistance readouts

    PMID:26725982

    Open questions at the time
    • How the same molecule partitions between Wnt-signaling and scaffolding pools is unknown
    • Structural basis of cavin-1/CAV1 binding not defined
  7. 2017 High

    Showed that despite being a pseudokinase, ROR1 can phosphorylate HER3 at Tyr1307 to drive a methylation-dependent YAP axis for bone metastasis, defining a distinct ErbB-independent effector mechanism.

    Evidence Phosphorylation assays, site-directed mutagenesis, MS, Co-IP, and in vivo bone metastasis models

    PMID:28114269

    Open questions at the time
    • Reconciliation with the catalytically-dead designation requires definition of how transphosphorylation enables this activity
    • Generality of the MAYA/NSUN6 axis across tumor types untested
  8. 2017 High

    Extended ROR1 function to physiological tissue regeneration, showing it is an NF-κB-induced effector required for satellite cell proliferation after muscle injury.

    Evidence Conditional SC-specific Ror1 knockout, cytokine-neutralizing antibodies, and NF-κB reporter assays in vivo

    PMID:28790171

    Open questions at the time
    • Downstream signaling driving satellite cell proliferation not mapped
    • Ligand context in regenerating muscle not identified
  9. 2018 High

    Pinpointed DOCK2 as the proline-rich-domain effector GEF and identified P808 as the single critical residue, providing precise molecular resolution to the Wnt5a-Rac axis.

    Evidence Point-mutagenesis (P808A), Co-IP, DOCK2 siRNA, Rac1/2 activation, and growth assays in CLL

    PMID:29678828

    Open questions at the time
    • Whether other GEFs use the same PRD site untested
    • How Wnt5a triggers PRD availability for DOCK2 unclear
  10. 2019 High

    Established HSP90α as a specific chaperone protecting ROR1 from proteasomal degradation, defining a druggable dependency for ROR1 stability.

    Evidence Co-IP/MS, paralog-specific analysis, ELHHPNIV motif mapping, and proteasome-rescue assays across two independent studies

    PMID:31726100 PMID:33370472

    Open questions at the time
    • Co-chaperones in the ROR1-HSP90 complex not identified
    • E3 ligase mediating ROR1 ubiquitination unknown
  11. 2019 High

    Added a second scaffolding function in which ROR1 binds CAVIN3 at a distinct site to control caveolae endocytosis and endosomal AKT signaling.

    Evidence Co-IP, domain-binding mapping, subcellular fractionation, and endocytosis/AKT assays in lung adenocarcinoma

    PMID:30894682

    Open questions at the time
    • Coordination between the CAV1, CAVIN1 and CAVIN3 binding events not resolved
    • Whether these scaffolding roles operate in the same cells as Wnt signaling unclear
  12. 2020 High

    Extended the DOCK2/P808 mechanism to ERK1/2 activation and showed it bypasses ibrutinib, explaining a route to therapy resistance.

    Evidence ROR1ΔPRD and P808A mutants, ERK1/2 phosphorylation assays, and pharmacological inhibition in CLL

    PMID:33097837

    Open questions at the time
    • Direct kinase linking DOCK2/Rac to ERK not defined
    • Clinical relevance of ibrutinib bypass not validated
  13. 2019 Medium

    Demonstrated tissue- and ligand-specific wiring of the Wnt5a-ROR1 GTPase output, with RhoA/DAAM1 dominating in esophageal cancer and Wnt16 ligand specificity in ALL.

    Evidence RhoA/DAAM1 activity assays, Co-IP ligand-specificity tests, and invasion assays in ESCC and TCF3-PBX1 ALL

    PMID:30631148 PMID:31114334

    Open questions at the time
    • Determinants selecting RhoA versus Rac branches not defined
    • Reconciliation with the canonical DOCK2/Rac model incomplete
  14. 2023 High

    Identified IGFBP5 as a second ROR1 ligand that drives ROR1/HER2 heterodimerization and CREB-mediated transcription, expanding ROR1's ligand repertoire beyond Wnt5a.

    Evidence Co-IP binding, IGFBP5 knockdown/overexpression, CRISPR editing, RNA-seq, and PDX models in glioblastoma

    PMID:36949068

    Open questions at the time
    • Structural basis of IGFBP5-ROR1 binding undefined
    • Whether IGFBP5 and Wnt5a compete or cooperate untested
  15. 2023 Medium

    Placed ROR1 within transcriptional feed-forward circuits, showing YAP/BRD4-driven ROR1 expression sustains tumor-initiating cell programs through c-Myc/E2F/AURKB.

    Evidence ChIP/epigenomic analysis, ROR1 depletion, and tumor recurrence/metastasis assays in PDAC

    PMID:37096681

    Open questions at the time
    • Whether ROR1 signaling reciprocally reinforces YAP not established
    • Direct versus indirect c-Myc induction unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a catalytically-dead pseudokinase reconciles its documented transphosphorylation of HER3 and HER2 partners with its scaffolding and Wnt5a-GEF functions in a single structural and regulatory framework remains unresolved.
  • No integrated structural model of liganded ROR1 signaling complexes
  • Mechanism partitioning ROR1 among Wnt-signaling, scaffolding, and transcriptionally-driven pools unknown
  • In vivo requirement of distinct functions in normal versus malignant tissue not separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0001618 virus receptor activity 2 GO:0060090 molecular adaptor activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005886 plasma membrane 2 GO:0005634 nucleus 1 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 2 R-HSA-5653656 Vesicle-mediated transport 2
Partners
CAV1CAVIN1CAVIN3CSNK1EDOCK2HSP90AA1ROR2TCL1
Complex memberships
caveolae

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 ROR1 interacts with casein kinase 1ε (CK1ε) to activate PI3K-mediated AKT phosphorylation and CREB, promoting breast cancer cell growth; Wnt5a-induced ROR1 signaling enhances this effect. Co-immunoprecipitation, siRNA silencing, in vitro/in vivo growth assays PloS one Medium 22403610
2016 Wnt5a induces ROR1 to oligomerize with ROR2 and recruit guanine nucleotide exchange factors (GEFs), activating Rac1 and RhoA to enhance CLL cell chemotaxis and proliferation; 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 GEF recruitment. Co-immunoprecipitation, siRNA silencing, ectopic expression of truncated/domain-deleted ROR1 constructs, Rac1/RhoA activation assays, in vivo engraftment The Journal of clinical investigation High 26690702
2017 ROR1 phosphorylates HER3 at Tyr1307 following neuregulin stimulation, independently of other ErbB family members; phospho-HER3 Tyr1307 then recruits the LLGL2-MAYA-NSUN6 RNA-protein complex to methylate Hippo/MST1 at Lys59, leading to MST1 inactivation and YAP target gene activation, promoting breast cancer bone metastasis. Biochemical phosphorylation assays, site-directed mutagenesis, mass spectrometry, Co-IP, in vivo bone metastasis models Nature cell biology High 28114269
2011 ROR1 is a pseudokinase devoid of intrinsic catalytic activity; in cancer cell lines with Met oncogene amplification, Met transphosphorylates ROR1; ROR1 suppression impairs proliferation in vitro and tumorigenesis in vivo in Met-amplified cells. Biochemical kinase assays, RNAi, Met inhibitor treatment, in vivo tumorigenesis assay Cancer research High 21487037
2013 ROR1 can complex with TCL1 in CLL cells (identified by immunoprecipitation and mass spectrometry); ROR1×TCL1 double-transgenic mice develop leukemia earlier with higher phospho-AKT, increased proliferation, and reduced apoptosis compared to TCL1 alone, demonstrating that ROR1 cooperates with TCL1 to enhance AKT signaling and leukemogenesis. Immunoprecipitation and mass spectrometry, transgenic mouse model, phospho-AKT measurement, adoptive transfer Proceedings of the National Academy of Sciences of the United States of America High 24379361
2018 Wnt5a induces ROR1 to complex with DOCK2 via the cytoplasmic proline-rich domain (PRD) of ROR1, activating Rac1/2; single amino acid substitution ROR1-P808A abolishes DOCK2 recruitment and Rac1/2 activation and abrogates the Wnt5a-driven growth advantage. Co-immunoprecipitation, truncation/point-mutagenesis of ROR1, siRNA silencing of DOCK2, Rac1/2 activation assays, cell proliferation assays Blood High 29678828
2020 Wnt5a induces ERK1/2 phosphorylation and CLL cell proliferation via a ROR1/DOCK2-dependent mechanism; ROR1 PRD (specifically P808) is required for Wnt5a-induced ERK1/2 and DOCK2 phosphorylation; ibrutinib cannot inhibit this Wnt5a-induced, ROR1-dependent ERK1/2 activation. siRNA silencing, ROR1 mutant (ROR1ΔPRD, ROR1P808A) transfection, ERK1/2 phosphorylation assays, pharmacological inhibition Leukemia High 33097837
2016 ROR1 functions as a scaffold protein for cavin-1 and caveolin-1 (CAV1) at the plasma membrane, independently of its kinase activity; this scaffold function prevents lysosomal degradation of CAV1, maintains caveolae structures, and sustains pro-survival AKT signaling from multiple RTKs (EGFR, MET, IGF-IR), contributing to EGFR-TKI resistance. Co-immunoprecipitation, ROR1 kinase-dead mutant analysis, immunofluorescence/electron microscopy of caveolae, AKT signaling assays, siRNA knockdown Nature communications High 26725982
2019 ROR1 possesses an additional scaffold function: it binds CAVIN3 at a site distinct from sites for CAV1 and CAVIN1, which is required for proper CAVIN3 subcellular localization and caveolae-dependent endocytosis; this ROR1-CAVIN3 interaction links caveolae trafficking to RTK-mediated pro-survival AKT signaling in early endosomes in lung adenocarcinoma cells. Co-immunoprecipitation, domain-binding mapping, subcellular fractionation, functional endocytosis assay, AKT signaling assays Oncogene High 30894682
2011 ROR1 undergoes N-linked glycosylation (producing ~100, 115, and 130 kDa variants) and mono-ubiquitination; glycosylation is required for cell surface localization of the mature 130-kDa isoform and for Ror1-induced filopodia formation; inhibition of glycosylation prevents cell surface trafficking. N-glycosidase treatment, glycosylation inhibitors, ubiquitination assay, immunocytochemistry, flow cytometry of surface proteins Acta physiologica Medium 21481194
2012 In t(1;19) ALL, ROR1 and pre-B cell receptor (pre-BCR) define distinct but counterbalancing downstream signaling pathways that both converge on AKT phosphorylation; inhibition of pre-BCR signaling by dasatinib upregulates ROR1, partially restoring AKT phosphorylation, while silencing ROR1 accentuates dasatinib-induced killing. Genetic epistasis (siRNA silencing), dasatinib treatment, AKT phosphorylation assays, cell viability assays Cancer cell Medium 23153538
2013 ROR1 expression is associated with EMT in breast cancer; silencing ROR1 reduces vimentin, SNAIL-1/2, ZEB1 and increases E-cadherin, CK-19, and ZO-1 expression, impairing migration/invasion in vitro and metastasis in vivo; ectopic ROR1 in MCF-7 cells reduces E-cadherin and increases SNAIL-1/2 and vimentin. siRNA knockdown, ectopic overexpression, EMT marker immunoblot, migration/invasion assays, in vivo metastasis model Cancer research Medium 23771907
2011 Nuclear-localized ROR1 activation promotes actin stress fiber formation and increased cellular migration; activated nuclear ROR1 upregulates cytoskeleton-related genes including radixin (RDX), ezrin (EZR), SOS2, and caldesmon 1 (CALD1). Inducible nuclear-homing FKBP-ROR1 fusion system with synthetic dimerizer AP20187, gene expression microarray, functional migration assays Anticancer research Medium 22199287
2019 ROR1 is a client protein of HSP90α (but not HSP90β or GRP94); HSP90 inhibition (geldanamycin and derivatives) destabilizes and degrades ROR1 via the ubiquitin/proteasome pathway; the kinase domain of ROR1 (but not its kinase activity or N-glycosylation) is required for HSP90-dependent stabilization. A specific binding motif (ELHHPNIV) on ROR1 mediates HSP90 association. Co-immunoprecipitation, pharmacological HSP90 inhibition, proteasome inhibitor rescue, domain/motif analysis, cell proliferation assays Cancer science / Pharmacological research High 31726100 33370472
2017 ROR1 expression in satellite cells (SCs) after muscle injury is induced by TNF-α and IL-1β via NF-κB activation; SC-specific depletion of Ror1 decreases the number of Pax7-positive SCs after injury, demonstrating that Ror1 is required for satellite cell proliferation during skeletal muscle regeneration. In vivo muscle injury model, neutralizing antibodies against TNF-α/IL-1β, conditional SC-specific Ror1 knockout, flow cytometry, C2C12 cell NF-κB reporter assays The Journal of biological chemistry High 28790171
2019 In esophageal squamous cell carcinoma, Wnt5a promotes cell invasion via ROR1 and ROR2 receptors through DAAM1 activation and downstream RhoA (but not Rac1/Rac2) signaling; ROR1 strongly associates with ROR2; DAAM1 and PI3Kα/Akt are parallel downstream pathways of ROR1/ROR2 in Wnt5a-induced migration. Anti-ROR1 mAb, ROR2 shRNA, RhoA/DAAM1 activity assays, immunoprecipitation, fluorescent phalloidin staining, invasion assays Cancer management and research Medium 31114334
2023 IGFBP5 is identified as a ligand for ROR1; IGFBP5 binding facilitates ROR1/HER2 heterodimer formation, inducing CREB-mediated expression of ETV5 and FBXW9, thereby promoting glioblastoma stem cell invasion and tumorigenesis. Co-immunoprecipitation (IGFBP5-ROR1 binding), siRNA knockdown and ectopic overexpression of IGFBP5, patient-derived xenograft model, CRISPR/Cas9 gene editing, RNA sequencing Nature communications High 36949068
2023 ROR1 transcriptional expression in pancreatic cancer is dependent on YAP/BRD4 binding at an enhancer region; ROR1 promotes PDAC proliferation by activating E2F through c-Myc to induce Aurora kinase B (AURKB) expression; ROR1-high cells serve as tumor-initiating cells. ChIP/epigenomic analysis, ROR1 depletion, gene expression analysis, functional tumor recurrence/metastasis assays The EMBO journal Medium 37096681
2022 In metastatic castration-resistant prostate cancer, canonical Wnt/β-catenin signaling transcriptionally upregulates ROR1, which then enhances non-canonical responses to Wnt5a; APC genomic loss (but not epigenetic downregulation) is strongly associated with Wnt/β-catenin pathway activation and downstream ROR1 upregulation. IHC correlation, patient-derived xenograft treatment with Wnt synthesis inhibitor, transcriptomic analysis of clinical samples Cancer research Low 35131873
2020 MSC-derived CXCL16 upregulates ROR1 expression in MKN45 gastric cancer cells via CXCR6/STAT3 activation; ROR1 induction downstream of STAT3 promotes gastric cancer cell proliferation and migration in vitro and tumor formation in vivo. siRNA knockdown of CXCL16 in MSC, recombinant CXCL16 treatment, STAT3 reporter/signaling assay, in vivo co-injection xenograft with CXCL16 neutralizing antibody Cancer science Medium 32012403
2023 ROR1 activates a positive feedback loop with STAT3 in osteoarthritis chondrocytes: Wnt5a-induced ROR1 promotes STAT3 nuclear translocation, and STAT3 in turn binds the ROR1 promoter to upregulate ROR1 expression; this ROR1/STAT3 loop activates NF-κB signaling, causing catabolic imbalance and cartilage degeneration. siRNA knockdown, STAT3 luciferase reporter assay, ChIP of STAT3 at ROR1 promoter, immunofluorescence, in vivo DMM surgical OA model International immunopharmacology Medium 37343369
2022 Notch and hypoxia signaling pathways transcriptionally activate Ror1 in glioblastoma stem-like cells (GSCs); NICD and HIF-1α bind upstream regions of the Ror1 gene more efficiently under spheroid conditions; upregulated Ror1 then promotes Wnt5a-driven spheroid formation (stem cell-like properties) in GSCs. Notch/hypoxia pathway inhibition, NICD forced expression, ChIP of NICD/HIF-1α at Ror1 promoter, spheroid formation assay Cancer science Medium 36314076
2021 ROR1 physically interacts with HSP90α (identified by Co-IP); a specific binding motif on ROR1 (ELHHPNIV) is necessary for HSP90-facilitated stabilization; HSP90 inhibition leads to ROR1 degradation via ubiquitin/proteasome pathway, attenuating ROR1-dependent pro-survival signaling in CLL. Mass spectrometry-based screen for ROR1 partners, Co-IP validation, binding motif mapping, ubiquitin-proteasome pathway assay Pharmacological research High 31726100
2019 In TCF3-PBX1 BCP-ALL, Wnt5a-ROR1 signaling activates RhoA/Rac1 GTPases and upregulates STAT3, enhancing cell proliferation; Wnt16b also activates this RhoA/Rac1 cascade but Wnt16 does not interact with ROR1 in TCF3-PBX1 cells. RhoA/Rac1 activation assays, Co-IP (Wnt16/ROR1 interaction tested), siRNA knockdown of ROR1, STAT3 measurement, high-throughput drug sensitivity Oncogene Medium 30631148
2017 Targeting ROR1 in mantle cell lymphoma downregulates NF-κB p65; NF-κB pathway activation can antagonize ROR1-mediated apoptotic responses, identifying NF-κB as a resistance mechanism to ROR1 targeting. ROR1 silencing, NF-κB pathway analysis, high-throughput drug sensitivity testing, synergy analysis Blood advances Medium 29296874
2021 ROR1 expression in Alzheimer's disease cell models is reduced by Aβ1-42 treatment; overexpressed ROR1 preserves the actin network, abrogates cytoskeletal protein degradation, and promotes neuritogenesis even in the presence of Aβ1-42; miR-146a and miR-34a repress ROR1 and are themselves regulated by lncRNA NEAT1. ROR1 overexpression in Aβ1-42 cell model, actin cytoskeleton imaging, RNA immunoprecipitation (NEAT1-miRNA interaction), miRNA overexpression Scientific reports Low 34584188

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Receptor affinity and extracellular domain modifications affect tumor recognition by ROR1-specific chimeric antigen receptor T cells. Clinical cancer research : an official journal of the American Association for Cancer Research 451 23620405
2017 A ROR1-HER3-lncRNA signalling axis modulates the Hippo-YAP pathway to regulate bone metastasis. Nature cell biology 268 28114269
2012 ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth. PloS one 234 22403610
2010 The B-cell tumor-associated antigen ROR1 can be targeted with T cells modified to express a ROR1-specific chimeric antigen receptor. Blood 226 20702778
2008 Unique cell surface expression of receptor tyrosine kinase ROR1 in human B-cell chronic lymphocytic leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research 207 18223214
2016 Wnt5a induces ROR1/ROR2 heterooligomerization to enhance leukemia chemotaxis and proliferation. The Journal of clinical investigation 162 26690702
2008 Ror1, a cell surface receptor tyrosine kinase is expressed in chronic lymphocytic leukemia and may serve as a putative target for therapy. International journal of cancer 154 18546292
2014 Safety of targeting ROR1 in primates with chimeric antigen receptor-modified T cells. Cancer immunology research 146 25355068
2013 Targeting ROR1 inhibits epithelial-mesenchymal transition and metastasis. Cancer research 145 23771907
2012 Crosstalk between ROR1 and the Pre-B cell receptor promotes survival of t(1;19) acute lymphoblastic leukemia. Cancer cell 140 23153538
2014 ROR1, an embryonic protein with an emerging role in cancer biology. Protein & cell 132 24752542
2001 Expression of the receptor tyrosine kinase genes, Ror1 and Ror2, during mouse development. Mechanisms of development 128 11429290
2016 High-level ROR1 associates with accelerated disease progression in chronic lymphocytic leukemia. Blood 125 27815263
2011 Ror1 is a pseudokinase that is crucial for Met-driven tumorigenesis. Cancer research 114 21487037
2001 Expression of the Ror1 and Ror2 receptor tyrosine kinase genes during mouse development. Development genes and evolution 108 11455430
2014 ROR1 expression correlated with poor clinical outcome in human ovarian cancer. Scientific reports 103 25056203
2015 Pre-clinical Specificity and Safety of UC-961, a First-In-Class Monoclonal Antibody Targeting ROR1. Clinical lymphoma, myeloma & leukemia 100 26297272
2015 IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas. PloS one 93 26173023
2021 Tyrosine Kinase ROR1 as a Target for Anti-Cancer Therapies. Frontiers in oncology 87 34123850
2014 The receptor tyrosine kinase ROR1--an oncofetal antigen for targeted cancer therapy. Seminars in cancer biology 86 25068995
2013 ROR1 can interact with TCL1 and enhance leukemogenesis in Eμ-TCL1 transgenic mice. Proceedings of the National Academy of Sciences of the United States of America 79 24379361
2016 ROR1 sustains caveolae and survival signalling as a scaffold of cavin-1 and caveolin-1. Nature communications 77 26725982
2022 ROR1: an orphan becomes apparent. Blood 73 35580162
2012 Orphan receptor tyrosine kinases ROR1 and ROR2 in hematological malignancies. Leukemia & lymphoma 68 22988987
2021 Zilovertamab Vedotin Targeting of ROR1 as Therapy for Lymphoid Cancers. NEJM evidence 66 38319241
2012 ROR1 and ROR2 in Human Malignancies: Potentials for Targeted Therapy. Frontiers in oncology 62 22655270
2011 ROR1 expression is not a unique marker of CLL. Hematological oncology 62 20597086
2015 Targeting the ROR1 and ROR2 receptors in epithelial ovarian cancer inhibits cell migration and invasion. Oncotarget 60 26515598
2013 The tyrosine kinase receptor ROR1 is constitutively phosphorylated in chronic lymphocytic leukemia (CLL) cells. PloS one 55 24205204
2020 Mesenchymal stem cell-derived CXCL16 promotes progression of gastric cancer cells by STAT3-mediated expression of Ror1. Cancer science 51 32012403
2020 Glucocorticoids induce differentiation and chemoresistance in ovarian cancer by promoting ROR1-mediated stemness. Cell death & disease 49 32989221
2016 Migration and invasion is inhibited by silencing ROR1 and ROR2 in chemoresistant ovarian cancer. Oncogenesis 49 27239958
2013 Inhibition of the receptor tyrosine kinase ROR1 by anti-ROR1 monoclonal antibodies and siRNA induced apoptosis of melanoma cells. PloS one 48 23593420
2023 IGFBP5 is an ROR1 ligand promoting glioblastoma invasion via ROR1/HER2-CREB signaling axis. Nature communications 47 36949068
2017 An ROR1 bi-specific T-cell engager provides effective targeting and cytotoxicity against a range of solid tumors. Oncoimmunology 45 28811962
2019 Wnt5a and ROR1 activate non-canonical Wnt signaling via RhoA in TCF3-PBX1 acute lymphoblastic leukemia and highlight new treatment strategies via Bcl-2 co-targeting. Oncogene 44 30631148
2018 Wnt5a induces ROR1 to recruit DOCK2 to activate Rac1/2 in chronic lymphocytic leukemia. Blood 44 29678828
2019 ROR1-targeted delivery of miR-29b induces cell cycle arrest and therapeutic benefit in vivo in a CLL mouse model. Blood 41 31151986
2019 Novel ROR1 inhibitor ARI-1 suppresses the development of non-small cell lung cancer. Cancer letters 39 31125641
2019 Molecular Mechanisms Associated with ROR1-Mediated Drug Resistance: Crosstalk with Hippo-YAP/TAZ and BMI-1 Pathways. Cells 39 31382410
2023 The signaling pathways activated by ROR1 in cancer. Cellular signalling 36 36621728
2022 Autocrine Canonical Wnt Signaling Primes Noncanonical Signaling through ROR1 in Metastatic Castration-Resistant Prostate Cancer. Cancer research 36 35131873
2020 ROR1 Is Expressed in Diffuse Large B-Cell Lymphoma (DLBCL) and a Small Molecule Inhibitor of ROR1 (KAN0441571C) Induced Apoptosis of Lymphoma Cells. Biomedicines 36 32586008
2017 Lnc-ing ROR1-HER3 and Hippo signalling in metastasis. Nature cell biology 36 28139652
2020 Wnt5a enhances proliferation of chronic lymphocytic leukemia and ERK1/2 phosphorylation via a ROR1/DOCK2-dependent mechanism. Leukemia 35 33097837
2025 Phase I Study of ROR1-Specific CAR-T Cells in Advanced Hematopoietic and Epithelial Malignancies. Clinical cancer research : an official journal of the American Association for Cancer Research 34 39466024
2011 Post-translational modifications regulate signalling by Ror1. Acta physiologica (Oxford, England) 32 21481194
2005 Comparative genomics on ROR1 and ROR2 orthologs. Oncology reports 32 16211313
2017 Silencing ROR1 and ROR2 inhibits invasion and adhesion in an organotypic model of ovarian cancer metastasis. Oncotarget 31 29348860
2010 Expression of ROR1 in patients with renal cancer--a potential diagnostic marker. Iranian biomedical journal 31 21079657
2018 ROR1 and ROR2 play distinct and opposing roles in endometrial cancer. Gynecologic oncology 30 29395309
2017 Targeting ROR1 identifies new treatment strategies in hematological cancers. Biochemical Society transactions 29 28408486
2023 YAP/BRD4-controlled ROR1 promotes tumor-initiating cells and hyperproliferation in pancreatic cancer. The EMBO journal 28 37096681
2015 Expression of ROR1, pAkt, and pCREB in gastric adenocarcinoma. Annals of diagnostic pathology 28 26245996
2022 ROR1-targeting switchable CAR-T cells for cancer therapy. Oncogene 26 35859167
2020 ROR1 is upregulated in endometrial cancer and represents a novel therapeutic target. Scientific reports 26 32807831
2017 Crosstalk between ROR1 and BCR pathways defines novel treatment strategies in mantle cell lymphoma. Blood advances 26 29296874
2017 The Ror1 receptor tyrosine kinase plays a critical role in regulating satellite cell proliferation during regeneration of injured muscle. The Journal of biological chemistry 25 28790171
2016 Targeting ROR1 inhibits the self-renewal and invasive ability of glioblastoma stem cells. Cell biochemistry and function 24 26923195
2024 Exosomal lncRNA ROR1-AS1 from cancer-associated fibroblasts inhibits ferroptosis of lung cancer cells through the IGF2BP1/SLC7A11 signal axis. Cellular signalling 23 38729321
2021 The ROR1 antibody-drug conjugate huXBR1-402-G5-PNU effectively targets ROR1+ leukemia. Blood advances 23 34424320
2017 Receptor tyrosine kinase-like orphan receptor 1 (ROR-1): An emerging target for diagnosis and therapy of chronic lymphocytic leukemia. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 22 28160756
2021 Receptor tyrosine kinase ROR1 ameliorates Aβ1-42 induced cytoskeletal instability and is regulated by the miR146a-NEAT1 nexus in Alzheimer's disease. Scientific reports 21 34584188
2019 Wnt5a induces ROR1 and ROR2 to activate RhoA in esophageal squamous cell carcinoma cells. Cancer management and research 21 31114334
2023 Anti-ROR1 CAR-T cells: Architecture and performance. Frontiers in medicine 20 36873868
2021 Perspectives on the development of antibody-drug conjugates targeting ROR1 for hematological and solid cancers. Antibody therapeutics 20 34805745
2018 ROR1 is highly expressed in circulating tumor cells and promotes invasion of pancreatic cancer. Molecular medicine reports 20 30272313
1997 Localization of the human Ror1 gene (NTRKR1) to chromosome 1p31-p32 by fluorescence in situ hybridization and somatic cell hybrid analysis. Genomics 20 9143508
2022 Developing ROR1 Targeting CAR-T Cells against Solid Tumors in Preclinical Studies. Cancers 19 35892876
2019 ROR1 Expression and Its Functional Significance in Hepatocellular Carcinoma Cells. Cells 19 30832318
2019 ROR1-CAVIN3 interaction required for caveolae-dependent endocytosis and pro-survival signaling in lung adenocarcinoma. Oncogene 19 30894682
2019 ROR1 and ROR2-novel targets for neuroblastoma. Pediatric hematology and oncology 19 31441359
2023 Design, synthesis, and biological evaluation of 6-(imidazo[1,2-a] pyridin-6-yl) quinazolin-4(3H)-one derivatives as potent anticancer agents by dual targeting Aurora kinase and ROR1. Bioorganic chemistry 18 36963371
2021 Predicting ROR1/BCL2 combination targeted therapy of small cell carcinoma of the lung. Cell death & disease 18 34088900
2017 Antiproliferative and Apoptotic Effects of Novel Anti-ROR1 Single-Chain Antibodies in Hematological Malignancies. SLAS discovery : advancing life sciences R & D 18 28328317
2011 Cytoskeleton network and cellular migration modulated by nuclear-localized receptor tyrosine kinase ROR1. Anticancer research 18 22199287
2025 A novel ROR1-targeting antibody-PROTAC conjugate promotes BRD4 degradation for solid tumor treatment. Theranostics 17 39816690
2024 Armored TGFβRIIDN ROR1-CAR T cells reject solid tumors and resist suppression by constitutively-expressed and treatment-induced TGFβ1. Journal for immunotherapy of cancer 17 38609317
2024 Discovery of Novel Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1) Inhibitors for Cancer Treatment. Journal of medicinal chemistry 17 38913699
2020 Upregulation of long non-coding RNA ROR1-AS1 promotes cell growth and migration in bladder cancer by regulation of miR-504. PloS one 17 31929567
2024 Therapeutic advances in the targeting of ROR1 in hematological cancers. Cell death discovery 16 39551787
2023 ROR1/STAT3 positive feedback loop facilitates cartilage degeneration in Osteoarthritis through activation of NF-κB signaling pathway. International immunopharmacology 16 37343369
2022 A ROR1 Small Molecule Inhibitor (KAN0441571C) Induced Significant Apoptosis of Mantle Cell Lymphoma (MCL) Cells. Pharmaceutics 16 36297673
2020 Functional and clinical significance of ROR1 in lung adenocarcinoma. BMC cancer 16 33172431
2019 Genetic interactions between Ror2 and Wnt9a, Ror1 and Wnt9a and Ror2 and Ror1: Phenotypic analysis of the limb skeleton and palate in compound mutants. Genes to cells : devoted to molecular & cellular mechanisms 16 30801848
2019 Wnt5a/ROR1 activates DAAM1 and promotes the migration in osteosarcoma cells. Oncology reports 16 31894282
2021 Inhibition of heat shock protein 90 destabilizes receptor tyrosine kinase ROR1 in lung adenocarcinoma. Cancer science 15 33370472
2021 SETD8 induces stemness and epithelial-mesenchymal transition of pancreatic cancer cells by regulating ROR1 expression. Acta biochimica et biophysica Sinica 15 34599596
2023 ROR1-STAT3 signaling contributes to ovarian cancer intra-tumor heterogeneity. Cell death discovery 14 37400436
2022 The Anti-ROR1 Monoclonal Antibody Zilovertamab Inhibits the Proliferation of Ovarian and Endometrial Cancer Cells. Pharmaceutics 14 35456672
2020 LncRNA ROR1-AS1 promotes colon cancer cell proliferation by suppressing the expression of DUSP5/CDKN1A. European review for medical and pharmacological sciences 14 32096171
2015 Spontaneous Immunity Against the Receptor Tyrosine Kinase ROR1 in Patients with Chronic Lymphocytic Leukemia. PloS one 14 26562161
2005 Identification and characterization of rat Ror1 and Ror2 genes in silico. International journal of molecular medicine 14 15702250
2024 Combinatorial immunotherapy with anti-ROR1 CAR NK cells and an IL-21 secreting oncolytic virus against neuroblastoma. Molecular therapy. Oncology 13 39895691
2023 Extracellular vesicle-associated tyrosine kinase-like orphan receptors ROR1 and ROR2 promote breast cancer progression. Cell communication and signaling : CCS 13 37430307
2022 Pressure increases PD-L1 expression in A549 lung adenocarcinoma cells and causes resistance to anti-ROR1 CAR T cell-mediated cytotoxicity. Scientific reports 13 35484298
2019 Long non-coding RNA ROR1-AS1 enhances colorectal cancer metastasis by targeting miR-375. European review for medical and pharmacological sciences 13 31486489
2019 Destabilization of ROR1 enhances activity of Ibrutinib against chronic lymphocytic leukemia in vivo. Pharmacological research 13 31726100
2022 Ror1 is expressed inducibly by Notch and hypoxia signaling and regulates stem cell-like property of glioblastoma cells. Cancer science 12 36314076
2020 Long noncoding RNA ROR1-AS1 enhances STC2-mediated cell growth and autophagy in cervical cancer through miR-670-3p. Journal of receptor and signal transduction research 12 33081599

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