Affinage

ROR1

Inactive tyrosine-protein kinase transmembrane receptor ROR1 · UniProt Q01973

Round 2 corrected
Length
937 aa
Mass
104.3 kDa
Annotated
2026-04-28
130 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ROR1 is a transmembrane pseudokinase receptor that transduces noncanonical Wnt signals to drive cell migration, survival, and proliferation across developmental and oncogenic contexts. Wnt5a binding induces ROR1 heterooligomerization with ROR2 via its extracellular Kringle domain, recruiting guanine nucleotide exchange factors (DOCK2 via Pro808, ARHGEF1 via Pro841 of the proline-rich domain) and adaptors (HS1, cortactin) to activate Rac1/2, RhoA, ERK1/2, NF-κB, and PI3K-AKT signaling cascades that promote EMT, invasion, and leukemic cell proliferation (PMID:26690702, PMID:29678828, PMID:30568170, PMID:23771907, PMID:33097837). Independent of its catalytically inactive kinase domain, ROR1 scaffolds cavin-1/caveolin-1 and CAVIN3 to maintain caveolae integrity and sustain RTK-mediated AKT signaling, and can phosphorylate HER3-Tyr1307 to recruit the LLGL2-MAYA-NSUN6 complex that inactivates the Hippo kinase MST1, promoting bone metastasis (PMID:26725982, PMID:30894682, PMID:28114269). Loss-of-function mutations in ROR1 cause autosomal recessive deafness through defective spiral ganglion neuron innervation of auditory hair cells (PMID:27162350).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 High

    Structural characterization of the ROR1 frizzled domain established it as an autonomously folded Wnt-binding module with a defined disulfide bonding pattern, providing the first biochemical foundation for understanding how ROR1 engages extracellular ligands.

    Evidence Recombinant expression, disulfide mapping, circular dichroism, and differential scanning calorimetry of the rat Ror1 FRZ domain

    PMID:11279007

    Open questions at the time
    • No ligand-bound structure determined
    • Binding affinity for Wnt ligands not measured
    • Contribution of other extracellular domains (Ig, Kringle) to ligand recognition not addressed
  2. 2005 Medium

    Demonstration that Ror1 (with Ror2) modulates neurite morphology and microtubule-associated protein expression in hippocampal neurons established a developmental neuronal function beyond the receptor's initial cloning as an orphan RTK.

    Evidence Antisense/RNAi knockdown and overexpression in hippocampal neurons with morphometric and MAP1B/MAP2 protein analysis

    PMID:15654020

    Open questions at the time
    • Ror1- vs Ror2-specific contributions not resolved
    • Upstream ligand not identified in this context
    • Downstream signaling mechanism not dissected
  3. 2012 High

    Identification of Wnt5a as a functional ligand and CK1ε as an intracellular partner of ROR1, together with demonstration that ROR1 sustains PI3K-AKT signaling through both kinase-dependent (c-Src) and kinase-independent (EGFR-ERBB3 scaffolding) mechanisms, established the dual signaling mode of ROR1 in cancer.

    Evidence Co-immunoprecipitation, siRNA knockdown, phosphoprotein analysis across lung adenocarcinoma cell lines and xenograft models

    PMID:22403610 PMID:22439932

    Open questions at the time
    • Direct kinase activity of human ROR1 not yet formally tested
    • Relative contributions of kinase-dependent vs -independent arms to in vivo tumor growth not quantified
  4. 2013 High

    ROR1 was shown to promote EMT (upregulating vimentin/SNAIL, downregulating E-cadherin) and to cooperate with TCL1 to enhance AKT-driven leukemogenesis in vivo, broadening the receptor's role from a signaling scaffold to a driver of tumor cell plasticity and oncogene cooperation.

    Evidence Gain/loss-of-function in breast cancer cells with in vivo metastasis assay; ROR1×TCL1 double-transgenic mice with accelerated leukemia and elevated phospho-AKT

    PMID:23771907 PMID:24379361

    Open questions at the time
    • EMT transcription factor directly downstream of ROR1 not identified
    • Whether TCL1-ROR1 interaction is direct or bridged not resolved
  5. 2014 High

    Biochemical demonstration that human ROR1 (and ROR2) kinase domains are catalytically deficient pseudokinases resolved a longstanding ambiguity and redirected mechanistic focus toward scaffolding and co-receptor functions.

    Evidence In vitro kinase assays with recombinant proteins and systematic mutagenesis of non-consensus residues

    PMID:25029443

    Open questions at the time
    • Conditions under which ROR1 might exhibit residual or context-dependent kinase activity not exhaustively tested
    • How the pseudokinase domain contributes structurally to signaling complex assembly not determined
  6. 2016 High

    Domain dissection revealed that Wnt5a-induced ROR1/ROR2 heterooligomerization requires the Kringle domain while GEF recruitment requires the cysteine-rich or proline-rich intracellular domain, defining a modular architecture for noncanonical Wnt signal transduction; separately, ROR1 was shown to scaffold cavin-1/caveolin-1 in a kinase-independent manner to maintain caveolae and RTK-AKT signaling; a causative ROR1 mutation (p.R736T) was linked to human deafness through loss of plasma membrane localization and NF-κB signaling.

    Evidence Truncation/mutation panels with Co-IP and GTPase assays; electron microscopy of caveolae with kinase-dead mutants; whole-exome sequencing of deaf patients with Ror1 mutant mouse phenotyping

    PMID:26690702 PMID:26725982 PMID:27162350

    Open questions at the time
    • Stoichiometry of ROR1/ROR2 oligomers unknown
    • How caveolae scaffolding and Wnt5a signaling are coordinated or segregated not addressed
    • Additional human ROR1 disease-causing alleles not reported
  7. 2017 High

    Residue-level mapping of the proline-rich domain identified Pro841 as the site for HS1 and ARHGEF1 recruitment (activating RhoA and migration) and revealed that ROR1 phosphorylates HER3-Tyr1307 to recruit the LLGL2-MAYA-NSUN6 complex, methylating MST1-Lys59 to inactivate Hippo signaling and drive bone metastasis — establishing two distinct downstream effector arms.

    Evidence Point mutants (P841A) with Co-IP and migration assays in CLL; phosphoproteomics, mutagenesis, complex reconstitution, and in vivo bone metastasis models

    PMID:28114269 PMID:28465529

    Open questions at the time
    • How ROR1 phosphorylates HER3 given its pseudokinase status is mechanistically unresolved — may require co-receptor kinase activity
    • Whether MST1 methylation pathway operates in non-metastatic contexts unknown
    • Structural basis for Pro841-mediated HS1 binding not determined
  8. 2018 High

    Pro808 of the PRD was mapped as the DOCK2-binding site required for Rac1/2 activation and proliferation, while cortactin was identified as a parallel PRD-Pro841-dependent effector whose Y421 phosphorylation recruits ARHGEF1 for RhoA-driven migration, establishing bifurcating signaling branches from distinct PRD residues.

    Evidence P808A point mutant with DOCK2 silencing and Rac activation assays; cortactin phosphorylation and F-actin assays in CLL cells

    PMID:29678828 PMID:30568170

    Open questions at the time
    • Whether Pro808 and Pro841 pathways are activated simultaneously or sequentially not resolved
    • Kinase responsible for cortactin Y421 phosphorylation downstream of ROR1 not identified
  9. 2019 High

    Extension of the cortactin-ARHGEF1-RhoA pathway to breast cancer metastasis in vivo, identification of CAVIN3 as an additional ROR1-scaffolded caveolae component, and demonstration that ROR1 signals through NF-κB to drive autocrine IL-6/STAT3 activation in CLL broadened the tissue scope and downstream signaling repertoire of ROR1.

    Evidence Xenograft metastasis models with cirmtuzumab; CAVIN3 domain mapping and EM; time-course signaling with NF-κB inhibitors and patient samples pre/post cirmtuzumab

    PMID:30894682 PMID:31409670 PMID:31667337

    Open questions at the time
    • Whether NF-κB activation requires GEF-Rho axis or is a parallel branch not determined
    • CAVIN3 binding site on ROR1 relative to cavin-1/CAV1 sites not mapped at residue level
  10. 2020 High

    Wnt5a-ROR1-DOCK2 signaling was shown to activate ERK1/2 independently of BTK, providing a mechanistic rationale for ibrutinib resistance in CLL and positioning the ROR1 pathway as a parallel survival axis.

    Evidence ERK1/2 phosphorylation assays with ibrutinib co-treatment, DOCK2 siRNA, and ROR1 P808A/ΔPRD mutants

    PMID:33097837

    Open questions at the time
    • Intermediate kinase(s) between DOCK2-Rac and ERK1/2 not identified
    • Clinical impact of dual BTK/ROR1 targeting not established mechanistically
  11. 2023 High

    IGFBP5 was identified as a second ROR1 ligand that promotes ROR1/HER2 heterodimer formation and CREB-mediated transcription in glioblastoma, while canonical Wnt/β-catenin signaling was shown to transcriptionally upregulate ROR1, creating a feedforward loop between canonical and noncanonical Wnt pathways.

    Evidence Co-IP and CRISPR-based functional studies with patient-derived xenografts for IGFBP5; ChIP-seq and PDX models for Wnt/β-catenin-ROR1 axis

    PMID:35131873 PMID:36949068

    Open questions at the time
    • Whether IGFBP5 and Wnt5a compete for ROR1 binding or engage different domains not tested
    • IGFBP5-ROR1 binding site not structurally resolved
    • Relative contributions of IGFBP5 vs Wnt5a signaling in physiological contexts unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for ROR1 pseudokinase-domain-mediated scaffolding, how ROR1 catalyzes HER3-Tyr1307 phosphorylation despite being catalytically deficient, whether the multiple ligands (Wnt5a, IGFBP5, resistin) activate distinct or overlapping downstream pathways, and the full physiological role of ROR1 outside oncology (e.g., in skeletal development and auditory innervation).
  • No full-length ROR1 structure available
  • Trans-phosphorylation mechanism for HER3 undefined
  • Developmental signaling partners remain uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 6 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 5
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 3
Partners
ARHGEF1CAV1CAVIN1CTTNDOCK2ERBB2HCLS1ROR2
Complex memberships
ROR1/HER2 heterodimerROR1/ROR2 heterooligomerROR1/cavin-1/caveolin-1/CAVIN3 caveolae complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 ROR1 interacts with casein kinase 1 epsilon (CK1ε) to activate PI3K-mediated AKT phosphorylation and CREB, and Wnt5a acts as a ligand for ROR1 to induce this ROR1-dependent signaling and enhance cancer cell growth. Co-immunoprecipitation, siRNA knockdown, in vitro growth assays, xenograft mouse models PloS one Medium 22403610
2012 NKX2-1/TTF-1 transcriptionally induces ROR1 expression in lung adenocarcinoma; ROR1 sustains prosurvival PI3K-AKT over pro-apoptotic p38 signaling through both kinase-dependent c-Src activation and kinase-independent maintenance of the EGFR-ERBB3 association and ERBB3 phosphorylation. siRNA knockdown, phosphoprotein analysis, co-immunoprecipitation, lung cancer cell line functional assays Cancer cell High 22439932
2013 ROR1 expression promotes epithelial-mesenchymal transition (EMT), enhancing vimentin and SNAIL-1/2 expression while reducing E-cadherin; silencing ROR1 attenuates in vitro migration/invasion and in vivo metastasis of breast cancer cells. siRNA/shRNA knockdown, overexpression in MCF-7 cells, Western blot for EMT markers, in vivo metastasis assay in immunodeficient mice, anti-ROR1 mAb treatment Cancer research High 23771907
2013 ROR1 complexes with TCL1 in CLL cells as revealed by immunoprecipitation and mass spectrometry; ROR1×TCL1 double-transgenic mice develop leukemia earlier than single-transgenic animals, with higher phospho-AKT levels, establishing ROR1 as an enhancer of TCL1-driven AKT signaling in leukemogenesis. Co-immunoprecipitation, mass spectrometry, transgenic mouse crosses, phospho-AKT analysis, adoptive transfer PNAS High 24379361
2014 Human ROR1 and ROR2 kinase domains are catalytically deficient (pseudokinases), whereas the C. elegans ortholog CAM-1 has active tyrosine kinase activity; substitution of non-consensus residues from ROR1/ROR2 into active kinases reduces activity, and restoration of consensus residues in ROR does not rescue kinase function. Additionally, the extracellular domain alone of ROR1 is sufficient to suppress canonical Wnt3a signaling. In vitro kinase assay with recombinant proteins, mutagenesis, Wnt reporter assays PloS one High 25029443
2001 The frizzled (FRZ) module of rat Ror1 contains 10 conserved cysteines forming disulfide bonds in a 1-5, 2-4, 3-8, 6-10, 7-9 pattern; the isolated domain forms a compact, stable folding unit with both alpha-helices and beta-strands. Recombinant protein expression in Pichia pastoris, proteolytic digestion, amino acid sequencing, circular dichroism, differential scanning calorimetry The Journal of biological chemistry High 11279007
2011 ROR1 is extensively modified by N-linked glycosylation, producing isoforms of ~100, 115, and 130 kDa; glycosylation is required for cell-surface localization of the 130 kDa isoform and for ROR1-induced filopodia formation. ROR1 is also mono-ubiquitinated. Glycosylation inhibitors, N-glycosidase treatment, immunohistochemistry, cell surface protein analysis, ubiquitination assay Acta physiologica Medium 21481194
2016 Wnt5a induces ROR1 to oligomerize with ROR2 and recruit guanine nucleotide exchange factors (GEFs), activating Rac1 and RhoA in CLL cells; the extracellular Kringle domain of ROR1 is required for ROR1/ROR2 heterooligomerization, and the cysteine-rich domain or intracellular proline-rich domain is required for GEF recruitment. Co-immunoprecipitation, siRNA silencing of ROR1/ROR2, domain truncation/mutation analysis, GTPase activation assays, xenograft mouse model The Journal of clinical investigation High 26690702
2016 ROR1 functions as a scaffold protein for cavin-1 (CAVIN1) and caveolin-1 (CAV1), facilitating their interaction at the plasma membrane in a kinase-independent manner; this prevents lysosomal degradation of CAV1, maintains caveolae structure, and sustains prosurvival AKT signaling through multiple RTKs including EGFR, MET, and IGF-IR. Co-immunoprecipitation, electron microscopy (caveolae structure), ROR1 kinase-dead mutants, lysosome inhibitor assays, lung cancer cell lines Nature communications High 26725982
2017 ROR1 phosphorylates HER3 at a previously unidentified site Tyr1307 following neuregulin stimulation, independently of other ErbB family members; phospho-HER3 Tyr1307 recruits the LLGL2-MAYA-NSUN6 RNA-protein complex to methylate Hippo/MST1 at Lys59, leading to MST1 inactivation and YAP target gene activation, promoting osteoclast differentiation and bone metastasis. Phosphoproteomic analysis, mutagenesis, co-immunoprecipitation, RNA-protein complex purification, methylation assays, in vivo bone metastasis models Nature cell biology High 28114269
2017 Wnt5a induces ROR1 to associate with HS1 (hematopoietic lineage cell-specific protein 1) via the ROR1 proline-rich domain (PRD); this complex recruits ARHGEF1 and activates RhoA, enhancing CLL cell migration. The proline at position 841 of the PRD is specifically required for HS1 and ARHGEF1 recruitment. Co-immunoprecipitation, domain truncation mutants, single amino-acid substitution mutants (P→A), GTPase activation assay, CLL cell migration assay Leukemia High 28465529
2018 Wnt5a induces ROR1 to recruit DOCK2 via the PRD (specifically Pro808), activating Rac1/2 and enhancing CLL cell proliferation. The ROR1P808A mutant cannot recruit DOCK2 or activate Rac1/2, and cells expressing it lack the proliferative advantage conferred by wild-type ROR1. Co-immunoprecipitation, siRNA silencing of DOCK2, single amino-acid substitution mutants (P808A), Rac1/2 activation assay, cell proliferation assay Blood High 29678828
2018 Wnt5a causes ROR1 to bind cortactin and induce tyrosine phosphorylation of cortactin at Y421, which recruits ARHGEF1 and activates RhoA to enhance CLL cell migration; the proline at position 841 of the ROR1 PRD is required for cortactin and ARHGEF1 recruitment. Co-immunoprecipitation, ROR1 PRD mutants (P→A), cortactin phosphorylation assay, F-actin polymerization assay, CLL migration assay Leukemia High 30568170
2019 Wnt5a-ROR1 signaling induces CLL cell NF-κB activation within 30 minutes, which in turn drives autocrine expression of IL-6 and other cytokines that subsequently induce STAT3 phosphorylation; cirmtuzumab blocks both NF-κB phosphorylation and STAT3 activation in patients treated with the antibody. Time-course signaling assays, NF-κB inhibitors, cytokine measurement, patient sample analysis before/after cirmtuzumab treatment Blood Medium 31409670
2019 Wnt5a induces ROR1 to recruit cortactin in breast cancer cells via PRD-Pro841; this complex phosphorylates cortactin at Y421, recruits ARHGEF1, activates RhoA, and promotes breast cancer cell migration and metastasis in vivo; cirmtuzumab inhibits cortactin phosphorylation in vivo. Co-immunoprecipitation, ROR1 point mutants, RhoA activation assay, in vivo xenograft metastasis model NPJ breast cancer High 31667337
2019 ROR1 functions as a scaffold for CAVIN3, binding at a site distinct from CAV1 and CAVIN1 binding sites; this interaction is required for proper CAVIN3 subcellular localization and caveolae-dependent endocytosis, which links to RTK-mediated prosurvival AKT signaling in early endosomes. Co-immunoprecipitation, domain mapping, electron microscopy, endocytosis assays, lung adenocarcinoma cell lines Oncogene High 30894682
2020 Wnt5a induces activation of ERK1/2 and enhances CLL cell proliferation via a ROR1/DOCK2-dependent pathway; this pathway is independent of BTK, as ibrutinib does not block Wnt5a-induced, ROR1-dependent ERK1/2 or DOCK2 phosphorylation. The ROR1P808A and ROR1ΔPRD mutants cannot support ERK1/2 activation. ERK1/2 phosphorylation assays, siRNA DOCK2 silencing, ibrutinib treatment, ROR1 point mutants, MEC1 transfection model Leukemia High 33097837
2011 Mouse resistin interacts with specific extracellular domains of ROR1, inhibits ROR1 phosphorylation, modulates ERK1/2 phosphorylation, regulates SOCS3, GLUT4, and GLUT1 expression, and promotes adipogenesis while modulating glucose uptake in 3T3-L1 cells through ROR1. Co-immunoprecipitation/binding assays, phosphorylation analysis, gene expression analysis, glucose uptake assay, adipogenesis assay in 3T3-L1 cells Molecular endocrinology Medium 22074948
2005 Ror1 and Ror2 modulate neurite elongation and branching in hippocampal neurons; Ror depletion (antisense or RNAi) results in shorter, less-branched minor processes and longer but less-branched axons, while Ror overexpression promotes short, highly branched processes; these phenotypes are accompanied by changes in microtubule-associated proteins MAP1B and MAP2. Antisense oligonucleotides, RNAi knockdown, overexpression in neurons and non-neuronal cells, morphometric analysis, MAP1B/MAP2 protein analysis Journal of cell science Medium 15654020
2016 Ror1-null mice display distinct skeletal and urogenital defects and postnatal growth retardation, demonstrating a non-redundant role for Ror1 in skeletal development and growth. Ror1 knockout mouse analysis, skeletal staining, anatomical phenotyping Developmental dynamics Medium 20593419
2016 ROR1 is essential for spiral ganglion neuron innervation of auditory hair cells and hearing; a missense mutation (p.R736T) prevents ROR1 from reaching the plasma membrane and abrogates WNT5A-induced NF-κB activation; Ror1 mutant mice are severely deaf with fasciculation defects in spiral ganglion axons and impaired Type I neuron synapses with inner hair cells. Whole-exome sequencing, cell localization assay, NF-κB reporter assay, Ror1 mutant mouse phenotyping, auditory testing (otoacoustic emissions, ABR), spiral ganglion histology PNAS High 27162350
2018 The 3D crystal structure of an ROR1-targeting scFv (R11) in complex with the kringle domain of ROR1 was determined at 1.6 Å resolution, precisely mapping a membrane-proximal epitope conserved between human and mouse ROR1. X-ray crystallography at 1.6 Å resolution PNAS High 29844189
2018 Twist transcription factor directly binds to and activates the ROR1 gene promoter, transcriptionally upregulating ROR1 expression; ROR1 silencing inhibits Twist-induced EMT, migration, invasion, and lung metastasis in basal-like breast cancer cells. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP), microarray transcriptomics, ROR1 siRNA knockdown, in vivo lung metastasis model Theranostics Medium 29774072
2023 IGFBP5 is identified as a ligand for ROR1; IGFBP5 binding to ROR1 facilitates ROR1/HER2 heterodimer formation, leading to CREB-mediated expression of ETV5 and FBXW9, thereby promoting glioblastoma stem cell invasion and tumorigenesis. Co-immunoprecipitation, IGFBP5 knockdown/overexpression, patient-derived xenograft model, RNA sequencing, CRISPR/Cas9 gene editing, nanocapsule delivery in orthotopic mouse model Nature communications High 36949068
2023 In pancreatic cancer, ROR1 induces expression of Aurora kinase B (AURKB) by activating E2F through c-Myc to enhance proliferation; ROR1 expression is transcriptionally dependent on YAP/BRD4 binding at an enhancer region. ROR1 depletion (siRNA/shRNA), ChIP-seq/epigenomic analysis, c-Myc and E2F pathway analysis, YAP/BRD4 inhibition, in vivo tumor growth and metastasis models The EMBO journal Medium 37096681
2020 CXCL16 produced by mesenchymal stem cells upregulates Ror1 expression in gastric cancer cells through activation of the CXCR6-STAT3 pathway; Ror1 expression in tumor cells is required for MSC-promoted tumor formation in vivo. siRNA knockdown of CXCL16, recombinant CXCL16 treatment, STAT3 pathway analysis, co-injection xenograft model, anti-CXCL16 neutralizing antibody Cancer science Medium 32012403
2023 ROR1 forms a positive feedback loop with STAT3 in osteoarthritis chondrocytes: Wnt5a-induced ROR1 activates NF-κB, and STAT3 binds the ROR1 promoter to upregulate ROR1 expression; ROR1 knockdown alleviates NF-κB activation and cartilage degradation in a surgical OA mouse model. Luciferase assay, immunofluorescence, Western blot, STAT3 ChIP on ROR1 promoter, DMM surgical OA mouse model, histological staining International immunopharmacology Medium 37343369
2022 Canonical Wnt/β-catenin signaling transcriptionally upregulates ROR1 expression in prostate cancer, and increased ROR1 enhances noncanonical responses to Wnt5a; APC genomic loss (but not epigenetic downregulation) is the key upstream driver of this pathway. Gene expression analysis, Wnt/β-catenin reporter assays, patient sample IHC, patient-derived xenograft treatment with Wnt synthesis inhibitor Cancer research Medium 35131873
2019 In esophageal squamous cell carcinoma, Wnt5a activates ROR1 (in complex with ROR2) to signal through DAAM1 and activate RhoA (but not Rac1/2), promoting actin filament reassembly and cell invasion; DAAM1 is positioned downstream of ROR1/ROR2 and upstream of RhoA in this pathway. Co-immunoprecipitation, DAAM1/ROR2 shRNA, Rho activation assay, immunofluorescence (phalloidin), cell invasion assay, DAAM1 rescue with wild-type overexpression Cancer management and research Medium 31114334
2017 COBLL1 is identified as a novel interaction partner of ROR1 in CLL cells; high COBLL1 expression correlates with impaired motility and enhanced BCR signaling (increased PLCγ2 and SYK phosphorylation after IgM stimulation). Co-immunoprecipitation/interaction studies, CLL patient sample analysis, chemotaxis assays, BCR signaling phosphorylation assays Haematologica Low 29122990

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2010 A large-scale, consortium-based genomewide association study of asthma. The New England journal of medicine 1582 20860503
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 A census of human transcription factors: function, expression and evolution. Nature reviews. Genetics 1191 19274049
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 610 16713569
1994 Isoform-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors. Genes & development 475 7926749
2011 Cryptochromes mediate rhythmic repression of the glucocorticoid receptor. Nature 467 22170608
2011 Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nature genetics 456 22001757
2014 Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. Nature 445 25231870
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2011 Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels. Circulation 426 21300955
2010 Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. Nature genetics 392 21102462
2010 Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 272 20072116
2017 A ROR1-HER3-lncRNA signalling axis modulates the Hippo-YAP pathway to regulate bone metastasis. Nature cell biology 266 28114269
2012 The human long non-coding RNA-RoR is a p53 repressor in response to DNA damage. Cell research 265 23208419
2010 Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 265 20375269
2001 The orphan nuclear receptor ROR alpha is a negative regulator of the inflammatory response. EMBO reports 239 11252722
2014 RORα and ROR γ are expressed in human skin and serve as receptors for endogenously produced noncalcemic 20-hydroxy- and 20,23-dihydroxyvitamin D. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 237 24668754
1993 Identification of nuclear receptor mRNAs by RT-PCR amplification of conserved zinc-finger motif sequences. Biochemical and biophysical research communications 236 7916608
1994 RZRs, a new family of retinoid-related orphan receptors that function as both monomers and homodimers. Molecular endocrinology (Baltimore, Md.) 235 7935491
2012 ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth. PloS one 234 22403610
2010 A genomewide association study of citalopram response in major depressive disorder. Biological psychiatry 233 19846067
1995 The nuclear receptor for melatonin represses 5-lipoxygenase gene expression in human B lymphocytes. The Journal of biological chemistry 231 7706239
2012 Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. PLoS genetics 222 22589738
2012 NKX2-1/TITF1/TTF-1-Induced ROR1 is required to sustain EGFR survival signaling in lung adenocarcinoma. Cancer cell 215 22439932
2012 EZH2 generates a methyl degron that is recognized by the DCAF1/DDB1/CUL4 E3 ubiquitin ligase complex. Molecular cell 208 23063525
2004 Crystal structure of the human RORalpha Ligand binding domain in complex with cholesterol sulfate at 2.2 A. The Journal of biological chemistry 198 14722075
1994 Cross-talk among ROR alpha 1 and the Rev-erb family of orphan nuclear receptors. Molecular endocrinology (Baltimore, Md.) 197 7838158
2008 Isoform-specific inhibition of ROR alpha-mediated transcriptional activation by human FOXP3. Journal of immunology (Baltimore, Md. : 1950) 194 18354202
2012 A genome-wide association study of post-traumatic stress disorder identifies the retinoid-related orphan receptor alpha (RORA) gene as a significant risk locus. Molecular psychiatry 179 22869035
2012 The onco-embryonic antigen ROR1 is expressed by a variety of human cancers. The American journal of pathology 172 23041612
2018 Phase I Trial: Cirmtuzumab Inhibits ROR1 Signaling and Stemness Signatures in Patients with Chronic Lymphocytic Leukemia. Cell stem cell 165 29859176
2019 ROR1-CAR T cells are effective against lung and breast cancer in advanced microphysiologic 3D tumor models. JCI insight 162 31415244
2016 Wnt5a induces ROR1/ROR2 heterooligomerization to enhance leukemia chemotaxis and proliferation. The Journal of clinical investigation 160 26690702
2014 Ovarian cancer stem cells express ROR1, which can be targeted for anti-cancer-stem-cell therapy. Proceedings of the National Academy of Sciences of the United States of America 156 25411317
2013 Targeting ROR1 inhibits epithelial-mesenchymal transition and metastasis. Cancer research 145 23771907
2014 Safety of targeting ROR1 in primates with chimeric antigen receptor-modified T cells. Cancer immunology research 143 25355068
2014 ROR1, an embryonic protein with an emerging role in cancer biology. Protein & cell 129 24752542
2016 High-level ROR1 associates with accelerated disease progression in chronic lymphocytic leukemia. Blood 125 27815263
2020 Inhibition of TGF-β-receptor signaling augments the antitumor function of ROR1-specific CAR T-cells against triple-negative breast cancer. Journal for immunotherapy of cancer 122 32303620
2019 Inhibition of chemotherapy resistant breast cancer stem cells by a ROR1 specific antibody. Proceedings of the National Academy of Sciences of the United States of America 116 30622177
2015 Pre-clinical Specificity and Safety of UC-961, a First-In-Class Monoclonal Antibody Targeting ROR1. Clinical lymphoma, myeloma & leukemia 100 26297272
2011 Mouse resistin modulates adipogenesis and glucose uptake in 3T3-L1 preadipocytes through the ROR1 receptor. Molecular endocrinology (Baltimore, Md.) 99 22074948
2012 Monoclonal antibodies against ROR1 induce apoptosis of chronic lymphocytic leukemia (CLL) cells. Leukemia 93 22289919
2015 IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas. PloS one 92 26173023
2014 The receptor tyrosine kinase ROR1--an oncofetal antigen for targeted cancer therapy. Seminars in cancer biology 86 25068995
2021 Tyrosine Kinase ROR1 as a Target for Anti-Cancer Therapies. Frontiers in oncology 85 34123850
2021 Tumor-derived exosomal circRNA_102481 contributes to EGFR-TKIs resistance via the miR-30a-5p/ROR1 axis in non-small cell lung cancer. Aging 81 33952725
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 78 24379361
2018 Twist promotes tumor metastasis in basal-like breast cancer by transcriptionally upregulating ROR1. Theranostics 75 29774072
2016 ROR1 sustains caveolae and survival signalling as a scaffold of cavin-1 and caveolin-1. Nature communications 75 26725982
2022 ROR1: an orphan becomes apparent. Blood 70 35580162
2011 ROR1 is expressed on hematogones (non-neoplastic human B-lymphocyte precursors) and a minority of precursor-B acute lymphoblastic leukemia. Leukemia research 70 21813176
2005 Neurite extension in central neurons: a novel role for the receptor tyrosine kinases Ror1 and Ror2. Journal of cell science 69 15654020
2012 Orphan receptor tyrosine kinases ROR1 and ROR2 in hematological malignancies. Leukemia & lymphoma 68 22988987
2010 Silencing of ROR1 and FMOD with siRNA results in apoptosis of CLL cells. British journal of haematology 66 20813009
2021 Zilovertamab Vedotin Targeting of ROR1 as Therapy for Lymphoid Cancers. NEJM evidence 64 38319241
2018 Potent and selective antitumor activity of a T cell-engaging bispecific antibody targeting a membrane-proximal epitope of ROR1. Proceedings of the National Academy of Sciences of the United States of America 63 29844189
2015 miR-382 inhibits migration and invasion by targeting ROR1 through regulating EMT in ovarian cancer. International journal of oncology 60 26575700
2012 Targeting malignant B cells with an immunotoxin against ROR1. mAbs 59 22531447
2019 Atractylenolide II reverses the influence of lncRNA XIST/miR-30a-5p/ROR1 axis on chemo-resistance of colorectal cancer cells. Journal of cellular and molecular medicine 55 30907503
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
2017 Wnt5a induces ROR1 to complex with HS1 to enhance migration of chronic lymphocytic leukemia cells. Leukemia 51 28465529
2019 Cirmtuzumab blocks Wnt5a/ROR1 stimulation of NF-κB to repress autocrine STAT3 activation in chronic lymphocytic leukemia. Blood 50 31409670
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
2023 IGFBP5 is an ROR1 ligand promoting glioblastoma invasion via ROR1/HER2-CREB signaling axis. Nature communications 45 36949068
2019 Strictinin, a novel ROR1-inhibitor, represses triple negative breast cancer survival and migration via modulation of PI3K/AKT/GSK3ß activity. PloS one 45 31150511
2017 An ROR1 bi-specific T-cell engager provides effective targeting and cytotoxicity against a range of solid tumors. Oncoimmunology 44 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 43 30631148
2005 RAR1, ROR1, and the actin cytoskeleton contribute to basal resistance to Magnaporthe grisea in barley. Molecular plant-microbe interactions : MPMI 43 15915638
2018 Wnt5a induces ROR1 to recruit DOCK2 to activate Rac1/2 in chronic lymphocytic leukemia. Blood 42 29678828
2016 ROR1 is essential for proper innervation of auditory hair cells and hearing in humans and mice. Proceedings of the National Academy of Sciences of the United States of America 42 27162350
2020 NF-κB-p62-NRF2 survival signaling is associated with high ROR1 expression in chronic lymphocytic leukemia. Cell death and differentiation 41 31992855
2019 ROR1-targeted delivery of miR-29b induces cell cycle arrest and therapeutic benefit in vivo in a CLL mouse model. Blood 41 31151986
2008 Overexpression of orphan receptor tyrosine kinase Ror1 as a putative tumor-associated antigen in Iranian patients with acute lymphoblastic leukemia. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 41 18354269
2020 Exosomal lncRNA ROR1-AS1 Derived from Tumor Cells Promotes Glioma Progression via Regulating miR-4686. International journal of nanomedicine 40 33204092
2019 Molecular Mechanisms Associated with ROR1-Mediated Drug Resistance: Crosstalk with Hippo-YAP/TAZ and BMI-1 Pathways. Cells 39 31382410
2019 Novel ROR1 inhibitor ARI-1 suppresses the development of non-small cell lung cancer. Cancer letters 38 31125641
2017 Lnc-ing ROR1-HER3 and Hippo signalling in metastasis. Nature cell biology 35 28139652
2017 Long non-coding RNA profile in mantle cell lymphoma identifies a functional lncRNA ROR1-AS1 associated with EZH2/PRC2 complex. Oncotarget 35 29113297
2021 The antibody drug conjugate VLS-101 targeting ROR1 is effective in CAR T-resistant mantle cell lymphoma. Journal of hematology & oncology 34 34454548
2018 Wnt5a causes ROR1 to complex and activate cortactin to enhance migration of chronic lymphocytic leukemia cells. Leukemia 34 30568170
2023 The signaling pathways activated by ROR1 in cancer. Cellular signalling 33 36621728
2022 Autocrine Canonical Wnt Signaling Primes Noncanonical Signaling through ROR1 in Metastatic Castration-Resistant Prostate Cancer. Cancer research 33 35131873
2020 Wnt5a enhances proliferation of chronic lymphocytic leukemia and ERK1/2 phosphorylation via a ROR1/DOCK2-dependent mechanism. Leukemia 32 33097837
2011 Post-translational modifications regulate signalling by Ror1. Acta physiologica (Oxford, England) 32 21481194
2010 Mice lacking the orphan receptor ror1 have distinct skeletal abnormalities and are growth retarded. Developmental dynamics : an official publication of the American Association of Anatomists 32 20593419
2005 Comparative genomics on ROR1 and ROR2 orthologs. Oncology reports 32 16211313
2018 miR‑30a inhibits epithelial‑mesenchymal transition and metastasis in triple‑negative breast cancer by targeting ROR1. Oncology reports 31 29693179
2017 Silencing ROR1 and ROR2 inhibits invasion and adhesion in an organotypic model of ovarian cancer metastasis. Oncotarget 31 29348860
2014 ROR1 as a novel therapeutic target for EGFR-mutant non-small-cell lung cancer patients with the EGFR T790M mutation. Translational lung cancer research 31 25806291
2018 ROR1 and ROR2 play distinct and opposing roles in endometrial cancer. Gynecologic oncology 30 29395309
2019 Wnt5a induces ROR1 to recruit cortactin to promote breast-cancer migration and metastasis. NPJ breast cancer 29 31667337
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 28 39466024
2015 Expression of ROR1, pAkt, and pCREB in gastric adenocarcinoma. Annals of diagnostic pathology 28 26245996
2014 Evolutionary divergence in the catalytic activity of the CAM-1, ROR1 and ROR2 kinase domains. PloS one 28 25029443
2001 Localization of disulfide bonds in the frizzled module of Ror1 receptor tyrosine kinase. The Journal of biological chemistry 28 11279007
2023 YAP/BRD4-controlled ROR1 promotes tumor-initiating cells and hyperproliferation in pancreatic cancer. The EMBO journal 27 37096681
2022 Inducible localized delivery of an anti-PD-1 scFv enhances anti-tumor activity of ROR1 CAR-T cells in TNBC. Breast cancer research : BCR 27 35659040
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
2022 ROR1-targeting switchable CAR-T cells for cancer therapy. Oncogene 25 35859167
2016 Targeting ROR1 inhibits the self-renewal and invasive ability of glioblastoma stem cells. Cell biochemistry and function 24 26923195
2021 The ROR1 antibody-drug conjugate huXBR1-402-G5-PNU effectively targets ROR1+ leukemia. Blood advances 23 34424320
2019 Ovarian Cancer Stem Cells with High ROR1 Expression Serve as a New Prophylactic Vaccine for Ovarian Cancer. Journal of immunology research 23 31008116
2024 Exosomal lncRNA ROR1-AS1 from cancer-associated fibroblasts inhibits ferroptosis of lung cancer cells through the IGF2BP1/SLC7A11 signal axis. Cellular signalling 22 38729321
2019 Wnt5a induces ROR1 and ROR2 to activate RhoA in esophageal squamous cell carcinoma cells. Cancer management and research 21 31114334
2015 ROR1-targeted delivery of OSU-2S, a nonimmunosuppressive FTY720 derivative, exerts potent cytotoxicity in mantle-cell lymphoma in vitro and in vivo. Experimental hematology 21 25937048
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
2023 Anti-ROR1 CAR-T cells: Architecture and performance. Frontiers in medicine 19 36873868
2020 Apoptotic effect of berberine via Bcl-2, ROR1, and mir-21 in patients with B-chronic lymphocytic leukemia. Phytotherapy research : PTR 19 33174291
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
2017 Antiproliferative and Apoptotic Effects of Novel Anti-ROR1 Single-Chain Antibodies in Hematological Malignancies. SLAS discovery : advancing life sciences R & D 18 28328317
2017 Expression of COBLL1 encoding novel ROR1 binding partner is robust predictor of survival in chronic lymphocytic leukemia. Haematologica 18 29122990
2017 Inhibition of tumor growth by mouse ROR1 specific antibody in a syngeneic mouse tumor model. Immunology letters 18 29175316
2022 Theranostic silk sericin/SPION nanoparticles for targeted delivery of ROR1 siRNA: Synthesis, characterization, diagnosis and anticancer effect on triple-negative breast cancer. International journal of biological macromolecules 17 36084874
2021 Predicting ROR1/BCL2 combination targeted therapy of small cell carcinoma of the lung. Cell death & disease 17 34088900
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 Wnt5a/ROR1 activates DAAM1 and promotes the migration in osteosarcoma cells. Oncology reports 16 31894282
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 15 38609317