Affinage

WNT5B

Protein Wnt-5b · UniProt Q9H1J7

Length
359 aa
Mass
40.3 kDa
Annotated
2026-06-11
66 papers in source corpus 32 papers cited in narrative 32 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

WNT5B is a secreted, post-translationally modified Wnt ligand that predominantly drives β-catenin-independent (non-canonical) signaling to control cell movement, differentiation, and migration across development and disease (PMID:20660632, PMID:27762090, PMID:34906330). Its secretion depends on N-linked glycosylation at three asparagines and lipidation at one serine, and on the cargo receptor Wntless; secreted WNT5B is delivered to target cells in active form via exosomes and via Ror2-loaded cytonemes (PMID:27762090, PMID:25934698, PMID:38123680). At the receptor level WNT5B engages Ryk, Frizzled-2/3, and ROR1/ROR2, channeling signal through Dishevelled (DVL2/3) recruitment to the membrane and activation of the small GTPases RAC1, CDC42, and RhoA, with downstream JNK, PKCα, CaMKII, and NFATc2 effectors (PMID:20660632, PMID:24220306, PMID:27036869, PMID:34906330, PMID:39094673). Through this PCP/calcium machinery WNT5B directs convergent-extension and gastrulation cell movements—requiring the GEF Def6, focal adhesion kinase, and the RGS3/Gα calcium module—and shapes chondrocyte and craniofacial cartilage morphogenesis (PMID:20660632, PMID:20628572, PMID:22039507, PMID:32097584, PMID:26459057). In several contexts WNT5B antagonizes canonical Wnt/β-catenin signaling, reducing nuclear β-catenin while promoting adipogenesis and suppressing osteoblast differentiation via the ROR1/ROR2–DVL–RAC1–CDC42–JNK–SIN3A axis (PMID:15796911, PMID:19577541, PMID:34906330); conversely it can act through FZD1/LRP6 to stabilize β-catenin in renal fibrosis and through canonical signaling to specify pacemaker cardiomyocytes (PMID:42256303, PMID:31402282). In cancer, WNT5B promotes migration, invasion, EndoMT, cancer stem-cell expansion, and metastasis through Cdc42/RhoA, JNK-driven MMP expression, ROR1–SOX2 stemness signaling, and a self-reinforcing PKCα–Rac1 loop (PMID:24220306, PMID:24841200, PMID:27121420, PMID:39094673, PMID:38689429). WNT5B also drives inflammatory and remodeling programs, inducing IL-6/CXCL8 via FZD2–TAK1–NF-κB, blood-brain-barrier disruption via ROR1–JNK–c-JUN repression of ZO-1, and neurodegenerative ECM damage via NFATc2–MMP14 (PMID:27036869, PMID:38896157, PMID:41549079).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2003 Medium

    Established that WNT5B has a developmental role distinct from the classic Ihh/PTHrP loop, controlling chondrocyte zone transitions through cell-cycle regulators.

    Evidence Mouse long-bone loss-of-function with cyclin D1, p130, and Col2a1 readouts

    PMID:12538525

    Open questions at the time
    • No receptor or signaling pathway identified
    • Mechanism of cyclin D1/p130 regulation undefined
  2. 2005 Medium

    Showed WNT5B can antagonize canonical Wnt/β-catenin signaling while promoting adipogenic differentiation, defining its non-canonical, anti-canonical character.

    Evidence Wnt5b overexpression in 3T3-L1 cells with nuclear β-catenin and Wnt3a co-treatment assays

    PMID:15796911

    Open questions at the time
    • Overexpression-based; endogenous role untested
    • Receptor mediating antagonism unknown
  3. 2009 Medium

    Refined the adipogenic mechanism to PPARγ/aP2 activation coupled with β-catenin suppression at adipogenesis initiation.

    Evidence Wnt5b overexpression in 3T3-L1 with PPARγ, aP2, and β-catenin readouts

    PMID:19577541

    Open questions at the time
    • Direct link between WNT5B receptor and PPARγ unresolved
    • Single-lab overexpression model
  4. 2010 High

    Identified Ryk as a WNT5B receptor distinct from Frizzled and dissected parallel directional-signaling and Dishevelled-recruitment branches during gastrulation.

    Evidence Zebrafish Ryk morpholino, Ca2+ imaging, directional migration co-culture, Dvl membrane recruitment

    PMID:20660632

    Open questions at the time
    • Biochemical WNT5B-Ryk binding not shown
    • How Ryk and Fzd2 outputs integrate unclear
  5. 2010 High

    Placed an RGS3/Gα calcium-regulating module downstream of WNT5B in somitogenesis, linking the ligand to G-protein-dependent Ca2+ dynamics.

    Evidence Zebrafish rgs3/wnt5b knockdown, Ca2+ imaging, Gα-interaction-deficient rescue

    PMID:20628572

    Open questions at the time
    • Identity of the relevant Gα and receptor not defined
    • Connection to PCP effectors unclear
  6. 2011 Medium

    Connected WNT5B to JNK/PCP control of chondrocyte hypertrophy and to Src-dependent β-catenin phosphorylation regulating cadherin turnover and condensation.

    Evidence Chondrogenic cultures with JNK and Src inhibitors, cadherin turnover and migration assays

    PMID:21413026

    Open questions at the time
    • Receptor not identified
    • Inhibitor-based pathway assignment, no genetic confirmation
  7. 2011 Medium

    Identified Def6 as a GEF acting downstream of WNT5B in convergent-extension movements, providing a molecular link to cytoskeletal regulation.

    Evidence Zebrafish morpholino with def6 epistasis rescue and Wnt11 double knockdown

    PMID:22039507

    Open questions at the time
    • Direct biochemical link from WNT5B to Def6 not shown
    • Morpholino-based
  8. 2013 Medium

    Established CNBP as a direct transcriptional repressor of wnt5b, identifying upstream regulation of ligand levels in development.

    Evidence Yeast one-hybrid, EMSA, ChIP, and zebrafish CNBP loss-of-function

    PMID:23667590

    Open questions at the time
    • Mammalian conservation of CNBP regulation untested
  9. 2013 Medium

    Demonstrated a pro-migratory role for WNT5B in carcinoma cells via activation of Cdc42 and RhoA GTPases.

    Evidence siRNA and recombinant protein in OSCC, GTPase activity and invasion assays

    PMID:24220306

    Open questions at the time
    • Receptor mediating GTPase activation unidentified
  10. 2014 Medium

    Revealed a WNT5B–PKCα positive feedback loop activating Rac1 to drive cytoskeletal reorganization and migration in transformed cells, with miR-200b as a brake.

    Evidence siRNA, forced PKCα expression, Rac1 assay, and 3'-UTR luciferase reporter in arsenic-transformed cells

    PMID:24841200

    Open questions at the time
    • Receptor link to PKCα not defined
    • Single transformation model
  11. 2015 Medium

    Defined WNT5B secretion as Wntless-dependent and linked it to fgf3 fine-tuning, and showed cooperation with Glypican 4 in cartilage morphogenesis.

    Evidence Zebrafish wnt5b/wls and gpc4 mutants, mRNA rescue, cell-autonomous transplants

    PMID:25934698 PMID:26459057

    Open questions at the time
    • Biochemical Gpc4-WNT5B interaction not shown
    • Receptor for fgf3 regulation unknown
  12. 2016 High

    Established the biochemical basis of WNT5B secretion (glycosylation, lipidation) and its delivery via exosomes, with downstream Dvl2 phosphorylation and Rac1 activation in cancer.

    Evidence PTM characterization of purified protein, CRISPR KO, TSG101 knockdown, immunoelectron microscopy in PANC-1

    PMID:27762090

    Open questions at the time
    • Receptor on recipient cells not defined here
    • Exosomal vs free ligand functional split unresolved
  13. 2016 Medium

    Expanded WNT5B's range to inflammatory and remodeling programs, defining FZD2-TAK1-NF-κB cytokine induction, EndoMT via Snail/Slug, JNK-MMP-driven CRC invasion, and TGF-β/Smad3 airway remodeling.

    Evidence Recombinant WNT5B with receptor/kinase knockdowns and inhibitors across fibroblasts, LECs, epithelial and CRC cells

    PMID:27036869 PMID:27121420 PMID:27126693 PMID:27593938

    Open questions at the time
    • Whether one or multiple receptors mediate these contexts unclear
    • Mostly exogenous-ligand single-lab studies
  14. 2018 Medium

    Positioned WNT5B in an IMP3–miR-145-5p axis feeding TAZ activation and SLUG transcription, linking the ligand to Hippo-pathway effector output.

    Evidence IMP3/miR-145-5p manipulation, mRNA stability and TAZ localization assays

    PMID:29847788

    Open questions at the time
    • Direct WNT5B-to-TAZ signaling mechanism not resolved
  15. 2018 Medium

    Showed WNT5B drives basal constriction at the midbrain-hindbrain boundary with Fak downstream and Gsk3β in the pathway.

    Evidence Zebrafish wnt5b/Fak knockdown, dominant-negative Gsk3β rescue, 3D cell reconstruction

    PMID:30305282

    Open questions at the time
    • Receptor not identified
    • Canonical vs non-canonical engagement of Gsk3β ambiguous
  16. 2019 High

    Demonstrated a context-specific canonical role: WNT5B/β-catenin directs Nkx2.5+ mesoderm to pacemaker cardiomyocyte fate, conserved to human PSCs.

    Evidence Zebrafish loss-of-function, lineage tracing, transcription factor readouts, hPSC directed differentiation

    PMID:31402282

    Open questions at the time
    • Receptor/co-receptor for canonical engagement not specified
    • Switch between canonical and non-canonical use unexplained
  17. 2020 Medium

    Linked WNT5B/Ryk to CaMKII-dependent P2X3 receptor trafficking and pain hypersensitivity, and showed Fak1a convergence on Rac1/Cdc42 in gastrulation.

    Evidence DRG neuron electrophysiology with Ryk antibody and CaMKII inhibitor; zebrafish fak1a cross-rescue with GTPase assays

    PMID:32097584 PMID:32979370

    Open questions at the time
    • Direct WNT5B-Ryk binding affinity unquantified
    • How CaMKII couples to P2X3 trafficking not detailed
  18. 2021 High

    Defined the ROR1/ROR2–DVL2/3–RAC1–CDC42–JNK–SIN3A axis by which WNT5B suppresses osteoblast differentiation, and identified ERα/NFATc1 enhancer (rs2887571) repression of WNT5B in patient osteoblasts.

    Evidence CRISPR allele editing, ChIP-qPCR, receptor/pathway manipulation, mineralization assays in 110 patient samples

    PMID:34906330

    Open questions at the time
    • Structural basis of ROR receptor engagement absent
    • Causal disease mutation not established
  19. 2021 Medium

    Connected WNT5B non-canonical signaling to mitochondrial fission driving VSMC proliferation/migration, antagonized by SFRP2-promoted fusion.

    Evidence Pulmonary artery SMC overexpression with mdivi-1 and SFRP2, mitochondrial morphology analysis

    PMID:34368954

    Open questions at the time
    • Receptor and signaling intermediate to fission machinery undefined
  20. 2023 High

    Revealed cytoneme-based intercellular transport: Wnt5b-Ror2 complexes assemble in producing cells and transfer on cytonemes to initiate PCP signaling in recipients independent of their own Ror2.

    Evidence Zebrafish live imaging, co-culture transfer assays with Ror2-deficient recipients, CE phenotype analysis

    PMID:38123680

    Open questions at the time
    • Recipient-cell receptor for transferred complex not defined
    • Relative contribution of cytonemes vs exosomes unresolved
  21. 2024 High

    Resolved receptor specificity across cancers—FZD3/DVL3-DEP/RAC1/JNK in NSCLC, Ror1 (not Ror2) in PDAC proliferation, and ROR1-SOX2/HYAL1 in osteosarcoma stemness and metastasis.

    Evidence Co-IP and DEP-domain deletion in NSCLC; CRISPR KO and xenografts in PANC-1; ROR1 antibody and PDX metastasis models

    PMID:38531660 PMID:38689429 PMID:39094673

    Open questions at the time
    • Why different ROR receptors dominate in different tissues unclear
    • FZD3-ROR co-receptor relationship not integrated
  22. 2024 Medium

    Implicated astrocyte-secreted WNT5B in blood-brain-barrier disruption via ROR1-JNK-c-JUN repression of the ZO-1 tight-junction promoter during infection.

    Evidence WNT5B treatment of BMECs, ROR1 manipulation, ZO-1 luciferase and c-JUN ChIP

    PMID:38896157

    Open questions at the time
    • In vivo BBB rescue by WNT5B blockade not shown
  23. 2026 Medium

    Extended WNT5B's pathological reach to renal fibrosis (exosomal FZD1/LRP6/β-catenin) and Huntington's disease (NFATc2-MMP14 ECM damage), with ERα and genistein as suppressors.

    Evidence In vivo hypoxia kidney model with exosome isolation and receptor identification; HD transgenic mice with NFATc2 reporters and pharmacological antagonism

    PMID:41549079 PMID:42256303

    Open questions at the time
    • Receptor for canonical renal signaling and NFATc2 upstream receptor not jointly defined
    • Single-lab in vivo models

Open questions

Synthesis pass · forward-looking unresolved questions
  • How WNT5B selects between canonical (β-catenin) and multiple non-canonical outputs in a given cell type, and the structural basis of its engagement with Ryk/ROR/Frizzled co-receptors, remains unresolved.
  • No structure of WNT5B-receptor complexes in the corpus
  • Determinants of canonical vs non-canonical pathway choice unknown
  • Relative in vivo roles of exosome vs cytoneme delivery undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0098772 molecular function regulator activity 4
Localization
GO:0005576 extracellular region 4 GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-1643685 Disease 5 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 2
Partners
DVL3FZD1FZD2FZD3LRP6ROR1ROR2RYK

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Wnt5b regulates the transition between different chondrocyte zones by differentially controlling cyclin D1 and p130 expression, as well as chondrocyte-specific Col2a1 expression, independently of the Ihh/PTHrP negative feedback loop. Genetic loss-of-function in mouse long bone development; expression analysis of cell cycle regulators Development Medium 12538525
2005 Wnt5b overexpression partially inhibits canonical Wnt/β-catenin signaling by reducing nuclear translocation of β-catenin, and promotes adipogenesis in 3T3-L1 preadipocytes, at least partly by antagonizing Wnt3a-induced canonical Wnt activation. Wnt5b overexpression in 3T3-L1 cells; microarray, RT-PCR, nuclear β-catenin localization assay, Wnt3a co-treatment rescue experiment Biochemical and biophysical research communications Medium 15796911
2009 Wnt5b stimulates adipogenesis by activating PPARγ and aP2 expression and inhibits β-catenin-dependent Wnt signaling at the initiation of adipogenesis in 3T3-L1 preadipocytes. Wnt5b overexpression in 3T3-L1 cells; measurement of PPARγ, aP2, and β-catenin translocation Biochemical and biophysical research communications Medium 19577541
2010 Wnt5b acts through the receptor Ryk (not solely Frizzled) to convey directional signals during zebrafish gastrulation; Ryk deficiency impairs Wnt5b-induced Ca2+ activity and directional cell movement, and Wnt5b-Ryk signaling promotes polarized cell protrusions. Fzd2, but not Ryk, recruits Dishevelled to the cell membrane upon Wnt5b stimulation, indicating separate downstream pathways. Zebrafish Ryk loss-of-function (morpholino); co-culture directional migration assay; Ca2+ imaging; cell membrane recruitment of Dishevelled assessed by imaging The Journal of cell biology High 20660632
2010 Rgs3 (Regulator of G protein Signaling 3) is required downstream of Wnt5b for appropriate frequency and amplitude of Ca2+ release during zebrafish somitogenesis; Rgs3 acts as a G protein GAP and its activity requires the ability to interact with Gα subunits. Zebrafish morpholino knockdown of rgs3 and wnt5b; in vivo Ca2+ imaging; rescue assays with Gα-interaction-deficient Rgs3 mutant PLoS genetics High 20628572
2011 Wnt5b inhibits chondrocyte hypertrophy and regulates chondroprogenitor cell migration through JNK activation (planar cell polarity pathway) and disrupts mesenchymal condensation via Src-dependent β-catenin phosphorylation leading to increased cadherin receptor turnover. Wnt5b expression in chondrogenic cultures; JNK inhibition (SP600125); Src inhibition; cadherin turnover assay; migration assay Journal of cellular physiology Medium 21413026
2011 Def6, a novel guanine nucleotide exchange factor (GEF), functions downstream of Wnt5b signaling to regulate convergent extension cell movements during zebrafish gastrulation; overexpression of def6 rescues Wnt5b morphant phenotypes. Zebrafish morpholino knockdown; genetic epistasis rescue (def6 overexpression rescues wnt5b morphants); double knockdown of def6 and Wnt11 PloS one Medium 22039507
2013 Wnt5b promotes cell motility (migration, invasion, filopodia formation) in oral squamous cell carcinoma cells through activation of Cdc42 and RhoA; siRNA knockdown of Wnt5b inhibits migration and filopodia, while recombinant Wnt5b stimulation increases active Cdc42 and RhoA levels. siRNA knockdown and recombinant protein stimulation; GTPase activity assays (active Cdc42, active RhoA); migration and invasion assays International journal of oncology Medium 24220306
2014 Wnt5b forms a positive feedback loop with PKCα in arsenic-transformed cells: Wnt5b sustains phospho-PKC levels, and PKCα in turn maintains Wnt5b expression. This Wnt5b-PKCα axis activates Rac1, promoting actin cytoskeletal reorganization and cell migration. miR-200b suppresses this pathway by directly targeting PKCα. siRNA knockdown of Wnt5b and PKCα; forced expression of PKCα in miR-200b-overexpressing cells; Rac1 activation assay; 3'-UTR luciferase reporter for miR-200b targeting PKCα The Journal of biological chemistry Medium 24841200
2016 Wnt5b is glycosylated at three asparagine residues and lipidated at one serine residue; these post-translational modifications are essential for Wnt5b secretion. Secreted Wnt5b phosphorylates Dvl2 and activates Rac1. In pancreatic cancer cells, ~55% of secreted endogenous Wnt5b is associated with exosomes, and Wnt5b-associated exosomes promote cancer cell migration and proliferation in a paracrine manner. Biochemical characterization of purified Wnt5b (glycosylation, lipidation); Wnt5b-KO PANC-1 cells (CRISPR); TSG101 knockdown; Dvl2 phosphorylation assay; Rac1 activation assay; centrifugation fractionation; immunoelectron microscopy; migration and proliferation assays Cancer science High 27762090
2016 WNT5B induces partial endothelial-mesenchymal transition (EndoMT) in lymphatic endothelial cells (LECs), promoting tube formation via upregulation of Snail and Slug transcription factors; WNT5B-induced Snail/Slug expression is abolished by IWR-1-endo (Wnt/β-catenin inhibitor) and Rac1 inhibitors, implicating both canonical and non-canonical (PCP) Wnt pathways. Recombinant WNT5B treatment of LECs; WNT5B knockdown in OSCC cells; tube formation, permeability, migration assays; phalloidin staining; SNAIL/SLUG knockdown; pathway inhibitors Oncogene Medium 27593938
2016 WNT5B signals through the Frizzled-2 receptor and TAK1 to induce IL-6 and CXCL8 release in lung fibroblasts via activation of JNK, p38, and p65 NF-κB, without involving canonical β-catenin signaling; IL-6 and CXCL8 release are controlled through distinct downstream pathways (JNK/p38 for both; IKK for CXCL8 only). Recombinant WNT5B treatment; Frizzled-2 knockdown; TAK1 inhibition; JNK, p38, IKK inhibitors; cytokine secretion measurement (ELISA); β-catenin pathway assessment American journal of physiology. Lung cellular and molecular physiology Medium 27036869
2016 WNT5B increases airway remodeling gene expression (fibronectin, MMP-2, MMP-9, Snail) in bronchial epithelial cells via TGF-β/Smad3 signaling. Exogenous WNT5B treatment of BEAS-2B and air-liquid interface PBECs; TGF-β/Smad3 pathway analysis The European respiratory journal Medium 27126693
2016 WNT5B promotes colorectal cancer cell migration and invasion through activation of the JNK signaling pathway, leading to increased MMP-2 and MMP-9 expression; JNK knockdown reverses these effects. Stable WNT5B overexpression in COLO 205 cells; JNK siRNA knockdown; MTT, wound healing, Transwell assays; western blot for MMP2/9 and JNK pathway Oncology reports Medium 27121420
2015 Wnt5b requires Wntless (Wls) for its secretion from pharyngeal tissue and regulates chondrogenic cell proliferation by fine-tuning fgf3 expression; fgf3 mRNA introduction rescues cartilage defects in Wnt5b- and Wls-deficient zebrafish larvae. Zebrafish wnt5b mutant and wls morphant analysis; fgf3 expression measurement; mRNA rescue experiment; cell proliferation and apoptosis assays Journal of cell science Medium 25934698
2015 Glypican 4 (Gpc4) and Wnt5b cooperate to regulate chondrocyte stacking and intercalation during craniofacial cartilage morphogenesis in zebrafish; Gpc4 functions cell-autonomously in chondrocytes, and double heterozygous wnt5b;gpc4 embryos show enhanced phenotype, suggesting genetic interaction independent of core Wnt/PCP molecules. Zebrafish wnt5b and gpc4 mutant analysis; cell-autonomous rescue with chimeric transplants; double heterozygous epistasis Mechanisms of development Medium 26459057
2015 Wnt5b and Wnt5a act through the JNK signaling pathway to mediate mechanical tension-induced osteogenic differentiation of rat tendon-derived stem cells; shRNA knockdown of Wnt5a/Wnt5b reduces UMT-induced Runx2 and P-JNK, and JNK activation rescues Runx2 expression. shRNA knockdown of Wnt5a and Wnt5b in rTDSCs; JNK inhibitor (SP600125) and activator (anisomycin); JNK1-shRNA and JNK1-cDNA; Runx2 and P-JNK protein measurement Cellular physiology and biochemistry Medium 25966835
2018 IMP3 stabilizes WNT5B mRNA indirectly by repressing miR-145-5p (which targets WNT5B), resulting in TAZ activation via alternative WNT signaling. WNT5B also facilitates SLUG transcription, which is required for TAZ nuclear localization. IMP3 knockdown/overexpression; miR-145-5p manipulation; WNT5B mRNA stability assay; TAZ nuclear localization; SLUG expression measurement Cell reports Medium 29847788
2019 Wnt5b signals through canonical Wnt (β-catenin) pathway in zebrafish to direct Nkx2.5+ mesoderm into pacemaker cardiomyocytes, activating transcription factors Isl1 and Tbx18 while silencing Nkx2.5; this mechanism is evolutionarily conserved and can be applied to direct human pluripotent stem cells toward pacemaker cardiomyocyte fate. Zebrafish Wnt5b loss-of-function; cell lineage tracing; transcription factor expression (Isl1, Tbx18, Nkx2.5); hPSC directed differentiation applying Wnt5b pathway findings Developmental cell High 31402282
2020 Wnt5b/Ryk signaling promotes membrane trafficking of P2X3 receptors to the DRG neuron surface via CaMKII activation, leading to enhanced P2X3 currents and pain hypersensitivity; anti-Ryk antibody and CaMKII inhibitor (KN93) block these effects. Wnt5b application to cultured DRG neurons; anti-Ryk antibody; CaMKII inhibitor KN93; electrophysiological recording of P2X3 currents; membrane P2X3 protein quantification; in vivo intrathecal injection Experimental neurology Medium 32979370
2020 Wnt5b and Fak1a (focal adhesion kinase 1a) converge in regulating Rac1 and Cdc42 to mediate gastrulation cell movements in zebrafish; overexpression of fak1a rescues wnt5b morphant convergence defects and vice versa, and Rac1/Cdc42 activation synergistically rescues both morphants. Zebrafish morpholino knockdown; CRISPR/Cas9 fak1a mutants; cross-rescue overexpression; Rac1 and Cdc42 activation measurement Open biology Medium 32097584
2021 WNT5B suppresses osteoblast differentiation and mineralization via ROR1/ROR2 receptors, which activate DVL2/3–RAC1–CDC42–JNK–SIN3A signaling and inhibit β-catenin activity; ERα and NFATc1 bind to an enhancer containing SNP rs2887571 to repress WNT5B expression, with the GG genotype showing greater ERα binding and greater WNT5B suppression than AA. ChIP-qPCR; CRISPR-Cas9 allele editing; ROR1/2 receptor manipulation; DVL2/3, RAC1, CDC42, JNK pathway analysis; alkaline phosphatase activity; mineralization assay; IL-6 measurement; correlation of genotype with WNT5B expression in 110 patient osteoblasts American journal of human genetics High 34906330
2021 WNT5B promotes VSMC proliferation and migration via non-canonical Wnt signaling and induces mitochondrial fission; inhibition of mitochondrial fission (by mdivi-1) abolishes WNT5B-induced VSMC proliferation and migration, while secreted frizzled-related protein 2 (SFRP2, a Wnt scavenger) attenuates VSMC proliferation/migration by promoting mitochondrial fusion. Primary pulmonary artery SMC culture; WNT5B overexpression; mitochondrial division inhibitor 1 (mdivi-1); SFRP2 treatment; proliferation and migration assays; mitochondrial morphology analysis Journal of cellular physiology Medium 34368954
2023 Wnt5b binds to Ror2 receptor in the producing cell; active Wnt5b-Ror2 complexes are loaded onto cytonemes (long cellular protrusions) and transferred to receiving cells, enabling initiation of Wnt-PCP signaling in recipient cells regardless of their own Ror2 status; this cytoneme-dependent spreading controls convergence and extension in zebrafish gastrula. Live imaging of Wnt5b-Ror2 on cytonemes in zebrafish; co-culture transfer assays; Ror2-deficient receiving cells; convergent extension phenotype analysis Nature High 38123680
2024 WNT5B signals through FZD3 receptor to recruit DVL3 to the plasma membrane (requiring DVL3's DEP domain) in a WNT5B ligand-dependent manner, activating JNK signaling via RAC1 (WNT-PCP pathway) to promote malignant phenotype of NSCLC cells; deletion of the DEP domain of DVL3 abrogates these effects. Co-IP of WNT5B-FZD3-DVL3; DVL3 DEP domain deletion mutant; membrane recruitment assay; JNK and RAC1 activation; in vivo and in vitro tumor assays Cellular signalling High 39094673
2024 Wnt5b signals through Ror1 (not Ror2) to promote PDAC cell proliferation in a cell-autonomous manner; knockdown of either Ror1 or Wnt5b in PANC-1 cells inhibits proliferation in vitro, and Ror1 knockout inhibits tumor growth in vivo. Ror1 and Wnt5b knockdown in PANC-1 cells; Ror1 CRISPR knockout; in vitro proliferation assays; in vivo xenograft tumor assay Genes to cells Medium 38531660
2024 WNT5B drives osteosarcoma cancer stem cell expansion and promotes lung/liver metastasis in vivo; WNT5B signals via ROR1 to induce SOX2 expression, and also upregulates HYAL1 to degrade hyaluronic acid in the tumor microenvironment; ROR1 antibody-mediated inhibition of WNT5B/ROR1 signaling reduces stemness, sphere size, and SOX2 expression. WNT5B overexpression and knockdown in osteosarcoma spheres and PDX; in vivo metastasis assay; ROR1 antibody treatment; SOX2, HYAL1 measurement; hyaluronic acid quantification Clinical and translational medicine Medium 38689429
2024 Astrocyte-secreted WNT5B activates non-canonical Wnt signaling in brain microvascular endothelial cells via receptor ROR1, leading to JNK/c-JUN activation; c-JUN directly binds to and represses the ZO-1 promoter, impairing tight junction integrity and disrupting the blood-brain barrier during meningitic E. coli infection. WNT5B treatment of BMECs; ROR1 pathway manipulation; dual luciferase reporter of ZO-1 promoter; ChIP for c-JUN binding; ZO-1 expression and tight junction measurement Molecular neurobiology Medium 38896157
2026 Astrocytic WNT5B activates NFATc2 transcription factor via non-canonical signaling, inducing sustained MMP14 expression, which degrades extracellular matrix, damages medium spiny neurons, and increases mutant huntingtin aggregation in Huntington's disease models; ERα overexpression suppresses NFATc2 transcriptional activity, and genistein antagonizes NFATc2 to reduce MMP14 transcription. WNT5B gain-of-function in HD transgenic mice (N171-82Q); NFATc2 reporter assays; MMP14 measurement; ERα overexpression; genistein treatment; motor behavior and lifespan analysis Signal transduction and targeted therapy Medium 41549079
2026 Wnt5b secreted by renal epithelial cells via exosomes activates canonical Wnt signaling in renal fibroblasts through cooperation of FZD1 and LRP6 receptors, triggering β-catenin cytoplasmic stabilization and nuclear translocation, driving fibroblast activation and renal fibrosis under hypoxia. Wnt5b knockdown in vivo (hypoxia mouse model); exosome isolation; FZD1 and LRP6 receptor identification; β-catenin nuclear translocation assay; fibroblast activation measurement iScience Medium 42256303
2013 CNBP transcription factor directly binds to the wnt5b gene locus and down-regulates wnt5b expression during zebrafish embryonic development, as confirmed by EMSA, ChIP, and loss-of-function experiments. Yeast one-hybrid; EMSA; ChIP; zebrafish CNBP loss-of-function with wnt5b expression measurement PloS one Medium 23667590
2018 Wnt5b is required for basal constriction at the zebrafish midbrain-hindbrain boundary (MHBC); focal adhesion kinase (Fak) acts downstream of Wnt5b in this process, functioning cell-autonomously within MHBC cells; dominant-negative Gsk3β expression overcomes wnt5b knockdown, placing Gsk3β in the pathway. Zebrafish wnt5b knockdown; Fak knockdown; tissue-specific Fak knockdown; dominant-negative Gsk3β rescue; Fak immunostaining; 3D reconstruction of MHBC cells Biology open Medium 30305282

Source papers

Stage 0 corpus · 66 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Wnt5a and Wnt5b exhibit distinct activities in coordinating chondrocyte proliferation and differentiation. Development (Cambridge, England) 328 12538525
2005 Wnt5b partially inhibits canonical Wnt/beta-catenin signaling pathway and promotes adipogenesis in 3T3-L1 preadipocytes. Biochemical and biophysical research communications 129 15796911
2004 Association of the gene encoding wingless-type mammary tumor virus integration-site family member 5B (WNT5B) with type 2 diabetes. American journal of human genetics 126 15386214
2016 Wnt5b-associated exosomes promote cancer cell migration and proliferation. Cancer science 123 27762090
2001 Molecular cloning and characterization of human WNT5B on chromosome 12p13.3 region. International journal of oncology 113 11445850
2009 Wnt5b stimulates adipogenesis by activating PPARgamma, and inhibiting the beta-catenin dependent Wnt signaling pathway together with Wnt5a. Biochemical and biophysical research communications 89 19577541
2019 Canonical Wnt5b Signaling Directs Outlying Nkx2.5+ Mesoderm into Pacemaker Cardiomyocytes. Developmental cell 78 31402282
2016 Tumour cell-derived WNT5B modulates in vitro lymphangiogenesis via induction of partial endothelial-mesenchymal transition of lymphatic endothelial cells. Oncogene 76 27593938
2010 Wnt5b-Ryk pathway provides directional signals to regulate gastrulation movement. The Journal of cell biology 69 20660632
2002 Expression and regulation of WNT5A and WNT5B in human cancer: up-regulation of WNT5A by TNFalpha in MKN45 cells and up-regulation of WNT5B by beta-estradiol in MCF-7 cells. International journal of molecular medicine 68 12165812
2014 MicroRNA-200b suppresses arsenic-transformed cell migration by targeting protein kinase Cα and Wnt5b-protein kinase Cα positive feedback loop and inhibiting Rac1 activation. The Journal of biological chemistry 60 24841200
2021 WNT5B in Physiology and Disease. Frontiers in cell and developmental biology 56 34017835
2019 WNT5B governs the phenotype of basal-like breast cancer by activating WNT signaling. Cell communication and signaling : CCS 56 31462314
2008 Analysis of the expression and function of Wnt-5a and Wnt-5b in developing and regenerating axolotl (Ambystoma mexicanum) limbs. Development, growth & differentiation 53 18336582
2011 Wnt5b regulates mesenchymal cell aggregation and chondrocyte differentiation through the planar cell polarity pathway. Journal of cellular physiology 52 21413026
2015 A role of glypican4 and wnt5b in chondrocyte stacking underlying craniofacial cartilage morphogenesis. Mechanisms of development 50 26459057
2016 Cigarette smoke-induced epithelial expression of WNT-5B: implications for COPD. The European respiratory journal 49 27126693
2005 Comparative genomics on Wnt5a and Wnt5b genes. International journal of molecular medicine 44 15754042
2016 Roles of Wnt pathway genes wls, wnt9a, wnt5b, frzb and gpc4 in regulating convergent-extension during zebrafish palate morphogenesis. Development (Cambridge, England) 41 27287801
2016 Distinct requirements of wls, wnt9a, wnt5b and gpc4 in regulating chondrocyte maturation and timing of endochondral ossification. Developmental biology 41 27908786
2016 Noncanonical WNT-5B signaling induces inflammatory responses in human lung fibroblasts. American journal of physiology. Lung cellular and molecular physiology 40 27036869
2023 Cytoneme-mediated transport of active Wnt5b-Ror2 complexes in zebrafish. Nature 39 38123680
2014 Mesenchymal-transitioned cancer cells instigate the invasion of epithelial cancer cells through secretion of WNT3 and WNT5B. Cancer science 37 24344732
2005 Overexpression of the Wnt5b gene in leiomyoma cells: implications for a role of the Wnt signaling pathway in the uterine benign tumor. The Journal of clinical endocrinology and metabolism 36 15972578
2015 Mechanical Tension Promotes the Osteogenic Differentiation of Rat Tendon-derived Stem Cells Through the Wnt5a/Wnt5b/JNK Signaling Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 35 25966835
2018 IMP3 Stabilization of WNT5B mRNA Facilitates TAZ Activation in Breast Cancer. Cell reports 34 29847788
2009 2.3 Mb terminal deletion in 12p13.33 associated with oculoauriculovertebral spectrum and evaluation of WNT5B as a candidate gene. European journal of medical genetics 33 19733267
2021 Exosome-mediated circ_0001846 participates in IL-1β-induced chondrocyte cell damage by miR-149-5p-dependent regulation of WNT5B. Clinical immunology (Orlando, Fla.) 32 34536574
2019 WNT5B exerts oncogenic effects and is negatively regulated by miR-5587-3p in lung adenocarcinoma progression. Oncogene 30 31666682
2013 Wnt5b promotes the cell motility essential for metastasis of oral squamous cell carcinoma through active Cdc42 and RhoA. International journal of oncology 30 24220306
2007 Human chorionic gonadotropin (hCG) up-regulates wnt5b and wnt7b in the mammary gland, and hCGbeta transgenic female mice present with mammary Gland tumors exhibiting characteristics of the Wnt/beta-catenin pathway activation. Endocrinology 27 17510243
2020 Wnt5b/Ryk-mediated membrane trafficking of P2X3 receptors contributes to bone cancer pain. Experimental neurology 26 32979370
2021 Estrogen receptor alpha and NFATc1 bind to a bone mineral density-associated SNP to repress WNT5B in osteoblasts. American journal of human genetics 24 34906330
2018 Basal constriction during midbrain-hindbrain boundary morphogenesis is mediated by Wnt5b and focal adhesion kinase. Biology open 23 30305282
2024 WNT5B drives osteosarcoma stemness, chemoresistance and metastasis. Clinical and translational medicine 22 38689429
2015 Control of Wnt5b secretion by Wntless modulates chondrogenic cell proliferation through fine-tuning fgf3 expression. Journal of cell science 21 25934698
2021 WNT5B in cellular signaling pathways. Seminars in cell & developmental biology 18 34635443
2010 Regulator of g protein signaling 3 modulates wnt5b calcium dynamics and somite patterning. PLoS genetics 18 20628572
2008 The effect of WNT5B IVS3C>G on the susceptibility to type 2 diabetes in UK Caucasian subjects. Nutrition, metabolism, and cardiovascular diseases : NMCD 18 18555673
2016 Overexpression of WNT5B promotes COLO 205 cell migration and invasion through the JNK signaling pathway. Oncology reports 17 27121420
2011 Def6 is required for convergent extension movements during zebrafish gastrulation downstream of Wnt5b signaling. PloS one 17 22039507
2013 Beyond the binding site: in vivo identification of tbx2, smarca5 and wnt5b as molecular targets of CNBP during embryonic development. PloS one 16 23667590
2021 WNT5B promotes vascular smooth muscle cell dedifferentiation via mitochondrial dynamics regulation in chronic thromboembolic pulmonary hypertension. Journal of cellular physiology 13 34368954
2014 Influence of adriamycin on changes in Nanog, Oct-4, Sox2, ARID1 and Wnt5b expression in liver cancer stem cells. World journal of gastroenterology 12 24944491
2018 Wnt5b regulates apoptosis in Litopenaeus vannamei against white spot syndrome virus. Fish & shellfish immunology 11 29325710
2022 Wnt5b plays a negative role in antibacterial response in Pacific white shrimp Penaeus vannamei. Developmental and comparative immunology 10 35447159
2020 Wnt5b integrates Fak1a to mediate gastrulation cell movements via Rac1 and Cdc42. Open biology 10 32097584
2024 Astrocytes-Secreted WNT5B Disrupts the Blood-Brain Barrier Via ROR1/JNK/c-JUN Cascade During Meningitic Escherichia Coli Infection. Molecular neurobiology 9 38896157
2024 WNT5B promotes the malignant phenotype of non-small cell lung cancer via the FZD3-DVL3-RAC1-PCP-JNK pathway. Cellular signalling 9 39094673
2019 Divergent effects of Wnt5b on IL-3- and GM-CSF-induced myeloid differentiation. Cellular signalling 9 31857239
2024 DLL4/Notch3/WNT5B axis mediates bidirectional prometastatic crosstalk between melanoma and lymphatic endothelial cells. JCI insight 8 37971882
2023 Paeoniflorin shows chondroprotective effects under IL-1β stress by regulating circ-PREX1/miR-140-3p/WNT5B axis. Journal of orthopaedic surgery and research 8 37817257
2017 Genetic Screening of WNT4 and WNT5B in Two Populations with Deviating Bone Mineral Densities. Calcified tissue international 7 28078366
2024 Targeting WNT5B and WNT10B in osteosarcoma. Oncotarget 6 39102216
2021 Understanding the binding affinities between SFRP1, SFRP1, Wnt and frizzled receptors 2, 3 and 7 using MD simulations. Journal of biomolecular structure & dynamics 5 33666148
2019 Insights into Molecular Interactions of human Wnt5b and Frizzled proteins for their role in teratogenicity. Bioinformation 4 31285641
2025 WNT5B regulates myogenesis and fiber type conversion by affecting mRNA stability. International journal of biological sciences 3 40612684
2024 Role of Wnt5b-Ror1 signaling in the proliferation of pancreatic ductal adenocarcinoma cells. Genes to cells : devoted to molecular & cellular mechanisms 3 38531660
2017 [Expression of Wnt5b in patients with HBV-related hepatocellular carcinoma and its clinical significance]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 2 28801288
2016 [The role of Wnt5b in the promotion of osteogenic differentiation by puerarin]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 1 27329882
2026 Astrocytic noncanonical WNT5B signaling modulates extracellular matrix remodeling and neuropathology in Huntington's disease. Signal transduction and targeted therapy 0 41549079
2026 Genome-Wide Characterization of the wnt Gene Family Reveals a wnt5b-Mediated Regulatory Mechanism of Testicular Development in Cynoglossus semilaevis. Animals : an open access journal from MDPI 0 41681368
2026 Giant cell tumor of bone inhibits osteoblastogenesis via WNT5B. Journal of bone and mineral metabolism 0 41872383
2026 Wnt5b/FZD1/LRP6 signaling drives renal fibrosis by triggering cytoplasmic stabilization and nuclear translocation of β-catenin under hypoxia. iScience 0 42256303
2025 ITLN1 Improves Endothelial Dysfunction in Hypertensive Mice via Wnt5b-JNK Signaling. Hypertension (Dallas, Tex. : 1979) 0 41091903
2025 The SCD5 Gene Modulates Adipogenic Differentiation via the WNT5B Signaling Pathway in Xinjiang Brown Cattle. Animals : an open access journal from MDPI 0 41463832

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