Affinage

WNT1

Proto-oncogene Wnt-1 · UniProt P04628

Length
370 aa
Mass
41.0 kDa
Annotated
2026-06-11
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

WNT1 is a secreted morphogen that activates canonical Wnt/β-catenin signaling by inhibiting GSK-3β, leading to β-catenin stabilization and TCF/Lef-dependent transcription of target genes (PMID:10748202, PMID:23656646, PMID:23499309). Through this pathway WNT1 drives cell-cycle entry by stabilizing cyclin D1–CDK4 complexes (PMID:10748202) and induces transcriptional targets including connexin43, which in turn feeds back to limit β-catenin transactivation (PMID:10642594). In the developing mid-/hindbrain WNT1 functions within the isthmic organizer cross-regulatory network, acting downstream of Lmx1b and upstream of Fgf8 to control precursor proliferation, boundary patterning, and the specification and birthdating of midbrain dopaminergic neurons (PMID:12399317, PMID:17166916, PMID:23444360); in zebrafish it acts redundantly with Wnt10b to maintain Pax2.1/Fgf8 thresholds at the boundary (PMID:12591239). A major role is in bone: osteoblast- and mesenchyme-derived WNT1 signals in a short-range juxtacrine mode to promote osteoblast differentiation and suppress osteoclastogenesis, and this bone-anabolic activity proceeds independently of the canonical co-receptor LRP5, also engaging YAP/BMP signaling to drive fracture healing (PMID:30404864, PMID:30690791, PMID:36891752). Loss-of-function WNT1 mutations cause early-onset osteoporosis and osteogenesis imperfecta, with mutant protein impaired in activating β-catenin signaling and mineralization (PMID:23656646, PMID:23499309). WNT1 transcription is set by upstream regulators including the MTA1/Six3 repressor axis and DLX2 (PMID:20682799, PMID:32165291), and its protein abundance is enhanced post-transcriptionally by Mettl14-mediated m6A modification (PMID:35004673). Beyond canonical signaling, WNT1 transactivates ErbB1 via MMP-mediated ligand shedding (PMID:12612606) and triggers TAK1–HIPK2–NLK-dependent phosphorylation and proteasomal degradation of c-Myb (PMID:15082531). Context-dependent paracrine WNT1 also drives renal myofibroblast activation and fibrosis (PMID:26204899) and remodels the tumor immune microenvironment by silencing dendritic-cell chemokines to promote T-cell exclusion (PMID:30926812).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1999 High

    Established that WNT1 signaling is subject to direct extracellular antagonism, defining a negative-regulatory node distinct from intracellular components.

    Evidence Co-IP and TCF/Lef reporter assays showing sFRP FrzA binds WNT1 and blocks β-catenin stabilization

    PMID:10523516

    Open questions at the time
    • Binding interface on WNT1 not mapped
    • Selectivity over other Wnt ligands not exhaustively tested
  2. 2000 High

    Defined how WNT1 couples β-catenin signaling to cell-cycle progression, showing GSK-3β inhibition stabilizes cyclin D1 to drive S-phase entry.

    Evidence Overexpression in NIH-3T3 with GSK-3β kinase assay, cyclin D1 immunoblot, BrdU, dominant-negative rescue; plus Cx43 induction in cardiac myocytes

    PMID:10642594 PMID:10748202

    Open questions at the time
    • Direct vs indirect GSK-3β regulation not resolved
    • Cell-type generality of cyclin D1 response unaddressed
  3. 2002 Medium

    Placed WNT1 within the isthmic organizer cascade, downstream of Lmx1b and upstream of Fgf8, explaining its role in mid-/hindbrain patterning.

    Evidence RCAS retroviral misexpression and in situ hybridization epistasis in chick; FGF8-bead induction of Lmx1b

    PMID:10751174 PMID:12399317

    Open questions at the time
    • Gain-of-function only; loss-of-function not tested in this system
    • Direct vs indirect Fgf8 induction unresolved
  4. 2004 High

    Revealed non-canonical WNT1 outputs: ErbB1 transactivation via MMP-mediated ligand shedding and TAK1–HIPK2–NLK-driven c-Myb degradation.

    Evidence Conditioned media, MMP inhibitors and ErbB1-blocking antibody; Co-IP, kinase, ubiquitination and proteasome-rescue assays

    PMID:12612606 PMID:15082531

    Open questions at the time
    • Receptor/co-receptor link from WNT1 to TAK1 activation not defined
    • Physiological context of ErbB1 transactivation limited to mammary cells
  5. 2006 High

    Demonstrated in vivo that WNT1 controls precursor proliferation and dose-dependent expansion of mid-/hindbrain territories, and that Lmx1b is genetically required to maintain Wnt1 expression.

    Evidence En1-promoter Wnt1 transgenic mice with cell-cycle analysis; Lmx1b conventional and conditional knockout with in situ readouts

    PMID:15121182 PMID:17166916

    Open questions at the time
    • Mechanism of cell-cycle shortening unresolved
    • Target genes mediating proliferation not identified
  6. 2013 High

    Established WNT1 as a temporally staged regulator of midbrain dopaminergic neuron specification and identified WNT1 loss-of-function mutations as a cause of human skeletal disease.

    Evidence Tamoxifen-inducible conditional Wnt1 deletion with lineage tracing; human family genetics with TOPflash and mineralization assays; zebrafish wnt1/wnt10b double-mutant epistasis

    PMID:12591239 PMID:23444360 PMID:23499309 PMID:23656646

    Open questions at the time
    • LRP5-dependence of skeletal signaling not yet tested here
    • Which downstream targets drive osteoblast vs neuronal phenotypes unresolved
  7. 2015 Medium

    Expanded WNT1 into coupling, fibrosis, fracture repair, and immune/survival contexts, showing paracrine and intracellular-effector versatility.

    Evidence Osteoclast TGF-βR knockout; proximal-tubule inducible Wnt1 transgenic; YAP/BMP fracture-healing model; macrophage CD36/PPAR-γ and microglial FoxO3a studies; MTA1/Six3 ChIP

    PMID:20462515 PMID:20682799 PMID:25721714 PMID:26108893 PMID:26204899 PMID:36891752

    Open questions at the time
    • Receptor identity in non-osteoblast contexts often undefined
    • Crosstalk between β-catenin and YAP/BMP or PPAR-γ not mechanistically dissected
  8. 2018 High

    Resolved that WNT1's bone-anabolic activity operates by short-range juxtacrine signaling and is independent of the canonical LRP5 co-receptor.

    Evidence Osteoblast- and mesenchyme-specific conditional KO/OE mice, LRP5 epistasis, juxtacrine vs paracrine co-culture, micro-CT and histomorphometry

    PMID:30404864 PMID:30690791

    Open questions at the time
    • Identity of the LRP5-independent receptor/co-receptor unknown
    • Molecular basis of juxtacrine restriction not defined
  9. 2019 High

    Identified tumor-derived WNT1 as an immunosuppressive signal that excludes T cells by reprogramming dendritic cells.

    Evidence Wnt1 gain/loss in murine LUAD, cDC and T-cell depletion epistasis, siWnt1-nanoparticles, intratumoral cDC transcriptomics

    PMID:30926812

    Open questions at the time
    • DC receptor mediating Wnt1 sensing unidentified
    • Direct vs β-catenin-independent mechanism in cDCs unresolved
  10. 2021 Medium

    Showed WNT1 abundance is set post-transcriptionally, with Mettl14-mediated m6A modification stabilizing WNT1 protein to confer cardioprotection.

    Evidence m6A MeRIP, Mettl14 KO mice, adenoviral overexpression, Wnt1 siRNA rescue, infarct/function readouts

    PMID:35004673

    Open questions at the time
    • Mechanism linking m6A to protein (not mRNA) levels unclear
    • Reader proteins not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • The receptor/co-receptor system mediating WNT1's LRP5-independent and non-osteoblast signaling, and how a single ligand selects between β-catenin, YAP/BMP, ErbB1, and kinase-cascade outputs, remain unresolved.
  • No defined receptor for LRP5-independent signaling
  • Determinants of output selection across tissues unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 4
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 2
Partners
FRZA

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 FrzA (a secreted frizzled-related protein, sFRP) specifically binds to WNT1 protein but not WNT5a, and this binding inhibits WNT1-mediated stabilization of cytoplasmic β-catenin and WNT1-induced transcription from a Lef/TCF reporter gene, acting as a negative regulator of WNT1 signaling. Co-immunoprecipitation, co-culture binding assays, β-catenin immunoblotting, TCF/Lef luciferase reporter assay Journal of Cell Science High 10523516
2000 WNT1 signaling in cardiac myocytes induces Cx43 (connexin43) mRNA and protein expression transcriptionally via β-catenin accumulation; the accumulated Cx43 co-localizes with β-catenin at junctional membranes and reduces β-catenin transactivation potential, creating a feedback mechanism. Co-culture with Wnt1-secreting cells, Li+ treatment mimicking Wnt signaling, Cx43 promoter-reporter transfection, Lucifer Yellow dye transfer, calcium wave propagation assay, immunolocalization The Journal of Clinical Investigation High 10642594
2000 WNT1 inhibits GSK-3β activity, leading to decreased cyclin D1 proteolysis and hyperaccumulation of active cyclin D1–CDK4 complexes; co-expression of WNT1 with activated MEK1 drives cyclin D1 accumulation and S-phase entry in the absence of serum growth factors, and a dominant-negative cyclin D1 mutant blocks this effect. Overexpression in NIH-3T3 cells, GSK-3β kinase assay, cyclin D1 immunoblotting, S-phase BrdU incorporation, dominant-negative cyclin D1 rescue The Journal of Biological Chemistry High 10748202
2003 Constitutive WNT1 expression in HC11 mammary epithelial cells activates TCF transcriptional activity and transactivates ErbB1 via MMP-mediated release of soluble ErbB1 ligands (blocked by anti-ErbB1 antibody and MMP inhibitors), leading to MAPK activation and increased cyclin D1 levels. Conditioned media transfer, ErbB1 phosphorylation assays, MMP inhibitor treatment, ErbB1-blocking antibody, MAPK assay, cyclin D1 immunoblot EMBO Reports Medium 12612606
2004 WNT1 signal causes nuclear entry of TAK1, which activates HIPK2 and NLK; NLK binds directly to c-Myb together with HIPK2, resulting in phosphorylation of c-Myb at multiple sites followed by ubiquitination and proteasome-dependent degradation, thereby suppressing c-Myb transcriptional activity. Co-immunoprecipitation, kinase assays, ubiquitination assay, proteasome inhibitor rescue, NLK overexpression in M1 cells Genes & Development High 15082531
2004 WNT1 cooperates with insulin/IGF signaling via GSK-3 inhibition to activate canonical Wnt/β-catenin signaling (nuclear β-catenin accumulation) in C2 myoblasts, promoting MyoD and myogenin expression, reserve cell activation, and myotube hypertrophy through increased reserve cell fusion. Co-culture with Wnt1-expressing fibroblasts, LiCl/SB216763 GSK-3 inhibition, nuclear β-catenin immunostaining, MyoD/myogenin immunofluorescence, myotube size quantification Molecular Biology of the Cell Medium 15282335
2004 Ectopic WNT1 expression in the caudal midbrain induces overproliferation of precursor cells in a gene dosage-dependent manner by shortening cell cycle length, and in adults promotes cell size increase specifically in neurons, demonstrating WNT1 acts as a regulator of proliferation of specific precursor populations in the mid-/hindbrain. Transgenic mice expressing Wnt1 under En1 promoter, BrdU/cell cycle length analysis, cell size morphometry, FACS Molecular and Cellular Neurosciences Medium 15121182
2005 In zebrafish hindbrain, Wnt1 (expressed at boundary and roof plate cells) activates proneural and delta gene expression to promote neurogenesis in non-boundary regions, and this neurogenesis/Notch-mediated lateral inhibition prevents ectopic boundary cell formation; Rfng modulates Notch signaling and is required for wnt1 expression at hindbrain boundaries. Morpholino knockdown of wnt1 and tcf3b, rfng knockdown, in situ hybridization for boundary markers (rfng, foxb1.2), epistasis analysis Development Medium 15659486
2000 The transcription factor Lmx1b maintains Wnt1 expression in the isthmic organizer: FGF8 induces Lmx1b expression, and Lmx1b in turn sustains Wnt1 expression; retroviral Lmx1b expression maintains Wnt1 in the mesencephalon, but ectopic Wnt1 does not recapitulate Lmx1b effects on mesencephalic morphology. In situ hybridization, FGF8-soaked bead implantation, RCAS retroviral misexpression of Lmx1b and Wnt1 in chick embryos Development Medium 10751174
2002 Misexpression of Lmx1b or Wnt1 in chick embryos causes expansion of tectum and cerebellum; Lmx1b induces Wnt1 expression, and Wnt1 in turn induces Fgf8 expression non-cell-autonomously, placing Wnt1 downstream of Lmx1b and upstream of Fgf8 in the isthmic organizer gene cascade. RCAS retroviral misexpression in chick, in situ hybridization for Fgf8, Wnt1, Lmx1b expression Development Medium 12399317
2006 Lmx1b is essential for Fgf8 and Wnt1 expression at the midbrain-hindbrain boundary: Lmx1b-/- embryos show complete absence of Fgf8 and downregulation of Wnt1 before the 4-somite stage; conditional region-specific knockout confirmed Lmx1b acts upstream of both Wnt1 and Fgf8 in the isthmic organizer cross-regulatory network. Lmx1b knockout mice, Wnt1-Cre conditional knockout, in situ hybridization, quantitative gene expression analysis Development High 17166916
2013 WNT1 missense mutations (p.Cys218Gly and p.Val355Phe identified in families with early-onset osteoporosis and osteogenesis imperfecta) show impaired capacity to induce canonical WNT/β-catenin signaling and target gene expression and mineralization in vitro; lineage tracing identified Wnt1 expression in osteocytes in mice. TOPflash luciferase reporter assay in cells transfected with mutant WNT1, mineralization assay, lineage tracing in mice The New England Journal of Medicine High 23499309 23656646
2013 Hypofunctional WNT1 alleles (frameshift, missense, splice-site, nonsense) cause failure to activate canonical LRP5-mediated WNT/β-catenin signaling; in vitro osteoblast differentiation shows enhanced Wnt1 expression with advancing differentiation, indicating a role in osteoblast function. Functional analysis of WNT1 variants in cell-based reporter assays; osteoblast differentiation assays American Journal of Human Genetics Medium 23499309
2018 Inactivation of Wnt1 specifically in osteoblasts causes severe osteoporosis and spontaneous fractures in mice, while conditional Wnt1 expression in osteoblasts increases osteoblast numbers and function; critically, the bone-anabolic effect of Wnt1 does not require LRP5, demonstrating Wnt1 can signal independently of this canonical co-receptor. Osteoblast-specific conditional knockout and conditional overexpression mouse models, micro-CT, histomorphometry, LRP5 knockout epistasis experiment Science Translational Medicine High 30404864
2019 Mesenchymal cell-derived WNT1 signals strictly in a juxtacrine (short-range) manner to induce osteoblast differentiation and suppress osteoclastogenesis, in part via canonical Wnt signaling; deletion of Wnt1 in limb mesenchymal progenitors leads to spontaneous fractures due to impaired osteoblast function and increased bone resorption. Global and limb-bud mesenchymal conditional Wnt1 knockout mice, co-culture juxtacrine vs. paracrine assays, histomorphometry, osteoclast differentiation assays Journal of Bone and Mineral Research High 30690791
2015 Osteoclast TGF-β receptor signaling induces Wnt1 expression in osteoclasts; osteoclast-specific inhibition of TGF-β receptor signaling reduces Wnt1 expression and osteoblast numbers, coupling bone resorption to formation via osteoclast-derived Wnt1. Osteoclast-specific TGF-β receptor knockout mice, Wnt1 expression analysis in osteoclasts, osteoblast number histomorphometry, TGF-β stimulation assays Journal of Bone and Mineral Research Medium 26108893
2015 Proximal tubule-specific inducible secretion of Wnt1 in mice is sufficient to drive interstitial myofibroblast activation, proliferation, and matrix protein production in kidneys without inflammatory cytokine expression or leukocyte infiltration, demonstrating that epithelial-derived Wnt1 drives renal fibrosis via paracrine canonical Wnt signaling. Inducible proximal-tubule Wnt1-expressing transgenic mouse, histology, myofibroblast marker staining, cytokine profiling, Wnt target gene expression in isolated PDGFR-β+ myofibroblasts Journal of the American Society of Nephrology High 26204899
2013 WNT1 in zebrafish acts redundantly with Wnt10b at the midbrain-hindbrain boundary (MHB): combined deletion/knockdown of wnt1 and wnt10b abolishes pax2.1, en2, and her5 expression in the ventral MHB; wnt1/wnt10b maintain threshold levels of Pax2.1 and Fgf8, and embryos deficient in both loci are sensitized to Pax2.1 or Fgf8 reduction. Deficiency allele generation, morpholino antisense knockdown, double-mutant epistasis with pax2.1 and fgf8 alleles, in situ hybridization Developmental Biology Medium 12591239
2013 Conditional deletion of Wnt1 at specific embryonic time points reveals an early requirement (1–6 somite stage) for all midbrain dopamine (MbDA) neuron specification: early Wnt1 deletion prevents LMX1a expression in the En1-derived domain and depletes MbDA neurons; a late requirement shows Wnt1 regulates birthdating and spatial distribution of MbDA neurons. Conditional Wnt1 allele, tamoxifen-inducible Cre-mediated deletion at defined time points, genetic lineage analysis, immunofluorescence for Lmx1a, OTX2, dopaminergic markers Development High 23444360
2010 MTA1s and MTA1 physically interact with Six3 chromatin; Six3 protein is a direct repressor of Wnt1 transcription (HDAC-dependent), and MTA1s/MTA1 relieve this repression by inhibiting Six3 transcription, thereby hyperactivating Wnt1 pathway; deletion of MTA1/MTA1s in MEFs upregulates Six3 and downregulates Wnt signaling. ChIP assay showing MTA1s/MTA1 on Six3 chromatin; gain- and loss-of-function of MTA1s/MTA1; Six3 knockout MEFs; Wnt1 promoter reporter assay; MTA1s/MTA1 knockout mouse mammary gland analysis Cancer Research Medium 20682799
2021 The m6A methyltransferase Mettl14 enhances Wnt1 protein levels (but not mRNA) through m6A modification of Wnt1 mRNA; Mettl14 overexpression prevents I/R-induced downregulation of Wnt1 and β-catenin, and knockdown of Wnt1 abrogates Mettl14-mediated cardioprotection. m6A MeRIP-seq/methylation assay, Mettl14 KO mice, adenovirus-mediated Mettl14 overexpression, Wnt1 siRNA rescue, infarct size and cardiac function assays Frontiers in Cell and Developmental Biology Medium 35004673
2019 Lung adenocarcinoma-derived paracrine Wnt1 signals to conventional dendritic cells (cDCs), causing transcriptional silencing of CC/CXC chemokines, T cell exclusion, and cross-tolerance; growth of murine lung adenocarcinomas dependent on cDCs and T cells is profoundly affected by altering Wnt1 expression, demonstrating immune microenvironment regulation by tumor-derived Wnt1. Wnt1 overexpression/silencing in murine LUAD models, cDC depletion, T cell depletion, siWnt1-nanoparticles, transcriptomic analysis of intratumoral cDCs, cytotoxicity assays Nature Communications High 30926812
2015 WNT1 boosts fracture healing by activating YAP/BMP signaling in osteoblasts within the fracture callus; osteoblast-specific inducible Wnt1 transgenic mice show accelerated fracture healing with increased BMP2 and activated YAP1; recombinant Wnt1 embedded in collagen gel also increases bone regeneration in critical-size bone defects. Osteoblast-specific inducible Wnt1 transgenic mice with femur osteotomy, transcriptome profiling, immunohistochemistry for YAP1 and BMP2, recombinant Wnt1 protein application Journal of Bone and Mineral Research Medium 36891752
2020 DLX2 transcription factor directly binds the WNT1 promoter (confirmed by ChIP assay) and activates Wnt1 transcription, thereby activating Wnt/β-catenin signaling and promoting osteogenic differentiation of human bone marrow mesenchymal stem cells; β-catenin inhibitor FH535 abolishes DLX2-enhanced osteogenesis. ChIP assay, DLX2 overexpression/knockdown, Wnt1 reporter, ALP activity assay, Alizarin Red mineralization, FH535 inhibitor rescue Gene Medium 32165291
2015 WNT1 activates canonical Wnt/β-catenin signaling in macrophages to upregulate CD36 expression via TCF4 and PPAR-γ; β-catenin interacts with PPAR-γ and both PPAR-γ and TCF4 co-localize in the nucleus; Pax3 transcription factor regulates Wnt1 by binding the first binding site in the Wnt1 promoter. siRNA knockdown of Wnt1, TCF4, PPAR-γ; β-catenin inhibitor; Co-immunoprecipitation; ChIP; immunofluorescence co-localization Cellular Physiology and Biochemistry Medium 25721714
2010 Wnt1 in inflammatory microglia prevents apoptosis during oxidative stress by promoting post-translational phosphorylation of FoxO3a to retain it in the cytoplasm, thereby blocking the FoxO3a-dependent apoptotic cascade (mitochondrial membrane permeability, cytochrome c release, Bad phosphorylation, caspase activation); NF-κB p65 is also required downstream of Wnt1 for microglial survival. Gene knockdown of Wnt1, FoxO3a, NF-κB p65; Wnt1 signaling blockade; subcellular fractionation; cytochrome c release assay; caspase activity assay; phospho-FoxO3a immunostaining Cellular Signalling Medium 20462515

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 WNT1-inducible signaling protein-1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis. The Journal of clinical investigation 477 19287097
2000 Wnt-1 regulation of connexin43 in cardiac myocytes. The Journal of clinical investigation 319 10642594
2013 WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta. The New England journal of medicine 292 23656646
2013 Mutations in WNT1 cause different forms of bone fragility. American journal of human genetics 223 23499309
2004 Wnt-1 signal induces phosphorylation and degradation of c-Myb protein via TAK1, HIPK2, and NLK. Genes & development 146 15082531
1992 Relationship between Wnt-1 and En-2 expression domains during early development of normal and ectopic met-mesencephalon. Development (Cambridge, England) 128 1360404
1991 Genomic structure and restricted neural expression of the zebrafish wnt-1 (int-1) gene. The EMBO journal 124 2009859
2004 Insulin and wnt1 pathways cooperate to induce reserve cell activation in differentiation and myotube hypertrophy. Molecular biology of the cell 120 15282335
2015 Paracrine Wnt1 Drives Interstitial Fibrosis without Inflammation by Tubulointerstitial Cross-Talk. Journal of the American Society of Nephrology : JASN 114 26204899
2004 Effects of Wnt1 signaling on proliferation in the developing mid-/hindbrain region. Molecular and cellular neurosciences 114 15121182
2003 Wnt1 and Wnt5a induce cyclin D1 expression through ErbB1 transactivation in HC11 mammary epithelial cells. EMBO reports 102 12612606
2000 The transcription factor Lmx1b maintains Wnt1 expression within the isthmic organizer. Development (Cambridge, England) 101 10751174
2010 WNT1-inducible signaling pathway protein-1 activates diverse cell survival pathways and blocks doxorubicin-induced cardiomyocyte death. Cellular signalling 98 20074638
2010 WNT1 inducible signaling pathway protein 1 (WISP1): a novel mediator linking development and disease. The international journal of biochemistry & cell biology 98 21109017
2015 MiR-148b suppresses cell proliferation and invasion in hepatocellular carcinoma by targeting WNT1/β-catenin pathway. Scientific reports 94 25627001
2002 Wnt-1 and Wnt-4 regulate thymic cellularity. European journal of immunology 93 11920562
2005 Wnt1 regulates neurogenesis and mediates lateral inhibition of boundary cell specification in the zebrafish hindbrain. Development (Cambridge, England) 91 15659486
2011 Erythropoietin and Wnt1 govern pathways of mTOR, Apaf-1, and XIAP in inflammatory microglia. Current neurovascular research 85 22023617
2002 Role of Lmx1b and Wnt1 in mesencephalon and metencephalon development. Development (Cambridge, England) 82 12399317
2019 Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma. Nature communications 81 30926812
2015 CCN4/WISP1 (WNT1 inducible signaling pathway protein 1): a focus on its role in cancer. The international journal of biochemistry & cell biology 80 25794425
2006 Lmx1b is essential for Fgf8 and Wnt1 expression in the isthmic organizer during tectum and cerebellum development in mice. Development (Cambridge, England) 80 17166916
2010 Wnt1, FoxO3a, and NF-kappaB oversee microglial integrity and activation during oxidant stress. Cellular signalling 78 20462515
2003 Wnt1 and wnt10b function redundantly at the zebrafish midbrain-hindbrain boundary. Developmental biology 76 12591239
2018 Wnt1 is an Lrp5-independent bone-anabolic Wnt ligand. Science translational medicine 74 30404864
2015 WNT1-induced Secreted Protein-1 (WISP1), a Novel Regulator of Bone Turnover and Wnt Signaling. The Journal of biological chemistry 73 25864198
2020 Targeting NEK2 impairs oncogenesis and radioresistance via inhibiting the Wnt1/β-catenin signaling pathway in cervical cancer. Journal of experimental & clinical cancer research : CR 71 32907622
2019 Quercetin suppresses the tumorigenesis of oral squamous cell carcinoma by regulating microRNA-22/WNT1/β-catenin axis. Journal of pharmacological sciences 71 31257059
1999 A secreted frizzled related protein, FrzA, selectively associates with Wnt-1 protein and regulates wnt-1 signaling. Journal of cell science 71 10523516
2015 Osteoclast TGF-β Receptor Signaling Induces Wnt1 Secretion and Couples Bone Resorption to Bone Formation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 68 26108893
2013 Hypoxic macrophages impair autophagy in epithelial cells through Wnt1: relevance in IBD. Mucosal immunology 68 24301659
2015 WNT-1 inducible signaling pathway protein-1 enhances growth and tumorigenesis in human breast cancer. Scientific reports 65 25732125
2000 Wnt1 and MEK1 cooperate to promote cyclin D1 accumulation and cellular transformation. The Journal of biological chemistry 65 10748202
2015 MicroRNA-148a inhibits breast cancer migration and invasion by directly targeting WNT-1. Oncology reports 62 26707142
2016 MiR-34a Inhibits Breast Cancer Proliferation and Progression by Targeting Wnt1 in Wnt/β-Catenin Signaling Pathway. The American journal of the medical sciences 61 27524218
2009 MMTV-Wnt1 and -DeltaN89beta-catenin induce canonical signaling in distinct progenitors and differentially activate Hedgehog signaling within mammary tumors. PloS one 61 19225568
2017 EET intervention on Wnt1, NOV, and HO-1 signaling prevents obesity-induced cardiomyopathy in obese mice. American journal of physiology. Heart and circulatory physiology 60 28576832
2007 Wnt1 and Wnt5a affect endothelial proliferation and capillary length; Wnt2 does not. Growth factors (Chur, Switzerland) 60 17454147
1995 Involvement of wnt1 and pax2 in the formation of the midbrain-hindbrain boundary in the zebrafish gastrula. Developmental genetics 60 7586754
2012 Wnt1 inducible signaling pathway protein 1 (WISP1) targets PRAS40 to govern β-amyloid apoptotic injury of microglia. Current neurovascular research 57 22873724
2020 LncRNA HOTTIP facilitates the stemness of breast cancer via regulation of miR-148a-3p/WNT1 pathway. Journal of cellular and molecular medicine 55 32307830
2003 Expression and regulation of WNT1 in human cancer: up-regulation of WNT1 by beta-estradiol in MCF-7 cells. International journal of oncology 55 12469206
2016 Skeletal Characteristics of WNT1 Osteoporosis in Children and Young Adults. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 52 27005318
2020 M2-like tumor-associated macrophages-secreted Wnt1 and Wnt3a promotes dedifferentiation and metastasis via activating β-catenin pathway in thyroid cancer. Molecular carcinogenesis 50 33283877
2018 miR-34b/c Regulates Wnt1 and Enhances Mesencephalic Dopaminergic Neuron Differentiation. Stem cell reports 49 29526736
2015 Functional analysis of Bombyx Wnt1 during embryogenesis using the CRISPR/Cas9 system. Journal of insect physiology 47 26070541
2011 Genome-wide analysis of a Wnt1-regulated transcriptional network implicates neurodegenerative pathways. Science signaling 47 21971039
2019 WNT1-inducible signaling pathway protein 1 (WISP1/CCN4) stimulates melanoma invasion and metastasis by promoting the epithelial-mesenchymal transition. The Journal of biological chemistry 46 30723155
2016 WNT1 Gene from WNT Signaling Pathway Is a Direct Target of miR-122 in Hepatocellular Carcinoma. Applied biochemistry and biotechnology 45 27687586
2014 Skeletal characteristics associated with homozygous and heterozygous WNT1 mutations. Bone 45 25010833
2013 Wnt1-regulated genetic networks in midbrain dopaminergic neuron development. Journal of molecular cell biology 43 24326514
2013 Periodic Wnt1 expression in response to ecdysteroid generates twin-spot markings on caterpillars. Nature communications 42 23673642
2019 Mesenchymal Cell-Derived Juxtacrine Wnt1 Signaling Regulates Osteoblast Activity and Osteoclast Differentiation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 41 30690791
2013 Dynamic temporal requirement of Wnt1 in midbrain dopamine neuron development. Development (Cambridge, England) 41 23444360
2021 Mettl14 Attenuates Cardiac Ischemia/Reperfusion Injury by Regulating Wnt1/β-Catenin Signaling Pathway. Frontiers in cell and developmental biology 40 35004673
2001 A possible role for the WNT-1 pathway in oral carcinogenesis. Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists 40 11345525
2014 Wnt5a-induced Wnt1-inducible secreted protein-1 suppresses vascular smooth muscle cell apoptosis induced by oxidative stress. Arteriosclerosis, thrombosis, and vascular biology 39 25212236
2018 Novel Regulatory Roles of Wnt1 in Infection-Associated Colorectal Cancer. Neoplasia (New York, N.Y.) 37 29626750
2019 Wnt1-inducible signaling protein 1 regulates laryngeal squamous cell carcinoma glycolysis and chemoresistance via the YAP1/TEAD1/GLUT1 pathway. Journal of cellular physiology 36 30805937
2012 WNT1-inducible signaling pathway protein 1 contributes to ventilator-induced lung injury. American journal of respiratory cell and molecular biology 36 22700866
2010 Metastasis-associated protein 1 and its short form variant stimulates Wnt1 transcription through promoting its derepression from Six3 corepressor. Cancer research 36 20682799
2018 MicroRNA‑301a targets WNT1 to suppress cell proliferation and migration and enhance radiosensitivity in esophageal cancer cells. Oncology reports 35 30365079
2015 Wnt1 Participates in Inflammation Induced by Lipopolysaccharide Through Upregulating Scavenger Receptor A and NF-kB. Inflammation 33 25749569
2018 MicroRNA-664-5p promotes myoblast proliferation and inhibits myoblast differentiation by targeting serum response factor and Wnt1. The Journal of biological chemistry 32 30323063
2004 Wnt1 inducible signaling pathway protein-3 regulation and microsatellite structure in arthritis. The Journal of rheumatology 31 15517620
2015 A WNT1-regulated developmental gene cascade prevents dopaminergic neurodegeneration in adult En1(+/-) mice. Neurobiology of disease 30 26049140
2023 Moshen granule ameliorates membranous nephropathy by blocking intrarenal renin-angiotensin system signalling via the Wnt1/β-catenin pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 29 37001295
2011 Molecular organization and timing of Wnt1 expression define cohorts of midbrain dopamine neuron progenitors in vivo. The Journal of comparative neurology 29 21713770
2018 Novel WNT1 mutations in children with osteogenesis imperfecta: Clinical and functional characterization. Bone 27 29935254
2018 Characterization of Wnt1-inducible Signaling Pathway Protein-1 in Obese Children and Adolescents. Current medical science 27 30341522
2017 Teriparatide Treatment in Patients With WNT1 or PLS3 Mutation-Related Early-Onset Osteoporosis: A Pilot Study. The Journal of clinical endocrinology and metabolism 27 27732335
2020 Biomarkers in WNT1 and PLS3 Osteoporosis: Altered Concentrations of DKK1 and FGF23. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 26 31968132
2015 Wnt1 positively regulates CD36 expression via TCF4 and PPAR-γ in macrophages. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 26 25721714
2013 Wnt1 inducible signalling pathway protein-2 (WISP‑2/CCN5): roles and regulation in human cancers (review). Oncology reports 25 24337439
2011 Wnt1 expression temporally allocates upper rhombic lip progenitors and defines their terminal cell fate in the cerebellum. Molecular and cellular neurosciences 25 22173107
2021 MiR-130a-3p suppresses colorectal cancer growth by targeting Wnt Family Member 1 (WNT1). Bioengineered 24 34657551
2020 Salidroside protects against diabetes mellitus-induced kidney injury and renal fibrosis by attenuating TGF-β1 and Wnt1/3a/β-catenin signalling. Clinical and experimental pharmacology & physiology 24 32472701
2020 Circle RNA FOXP1 promotes cell proliferation in lung cancer by regulating miR-185-5p/Wnt1 signaling pathway. European review for medical and pharmacological sciences 24 32633368
2019 UV irradiation-induced DNA hypomethylation around WNT1 gene: Implications for solar lentigines. Experimental dermatology 24 31020703
2019 Wnt1 Promotes EAAT2 Expression and Mediates the Protective Effects of Astrocytes on Dopaminergic Cells in Parkinson's Disease. Neural plasticity 24 31582965
2017 Impaired WNT signaling and the spine-Heterozygous WNT1 mutation causes severe age-related spinal pathology. Bone 24 28411110
2017 Association of Wnt1-inducible signaling pathway protein-1 with the proliferation, migration and invasion in gastric cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 23 28618940
2010 Cooperative signaling between Wnt1 and integrin-linked kinase induces accelerated breast tumor development. Breast cancer research : BCR 23 20565980
2010 Metastasis-associated protein 1 short form stimulates Wnt1 pathway in mammary epithelial and cancer cells. Cancer research 23 20710043
2023 Genotypic and Phenotypic Spectrum and Pathogenesis of WNT1 Variants in a Large Cohort of Patients With OI/Osteoporosis. The Journal of clinical endocrinology and metabolism 22 36595228
2005 Identification and characterization of rat Wnt1 and Wnt10b genes in silico. International journal of oncology 22 15703844
2024 Bufalin suppresses hepatocellular carcinogenesis by targeting M2 macrophage-governed Wnt1/β-catenin signaling. Phytomedicine : international journal of phytotherapy and phytopharmacology 21 38340578
2010 Pea3 transcription factors and wnt1-induced mouse mammary neoplasia. PloS one 21 20107508
2022 Wnt family member 1 (Wnt1) overexpression-induced M2 polarization of microglia alleviates inflammation-sensitized neonatal brain injuries. Bioengineered 20 35603707
2020 MiR-145-5p mitigates dysregulated Wnt1/β-catenin signaling pathway in rheumatoid arthritis. International immunopharmacology 20 32088641
2020 DLX2 activates Wnt1 transcription and mediates Wnt/β-catenin signal to promote osteogenic differentiation of hBMSCs. Gene 20 32165291
2020 MicroRNA-148a-3p suppresses epithelial-to-mesenchymal transition and stemness properties via Wnt1-mediated Wnt/β-catenin pathway in pancreatic cancer. Journal of cellular and molecular medicine 20 33026174
2019 Aspirin ameliorates lung cancer by targeting the miR-98/WNT1 axis. Thoracic cancer 20 30756509
2023 KLF3 Transcription Activates WNT1 and Promotes the Growth and Metastasis of Gastric Cancer via Activation of the WNT/β-Catenin Signaling Pathway. Laboratory investigation; a journal of technical methods and pathology 19 36827869
2023 Wnt1 Boosts Fracture Healing by Enhancing Bone Formation in the Fracture Callus. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 19 36891752
2021 Long noncoding RNA DLGAP1-AS2 facilitates Wnt1 transcription through physically interacting with Six3 and drives the malignancy of gastric cancer. Cell death discovery 19 34545072
2014 Sox9 regulates hyperexpression of Wnt1 and Fzd1 in human osteosarcoma tissues and cells. International journal of clinical and experimental pathology 19 25197350
2020 LncRNA HOXA11-AS promotes migration and invasion through modulating miR-148a/WNT1/β-catenin pathway in gastric cancer. Neoplasma 18 32009419
2020 Osteoblastic Wnt1 regulates periosteal bone formation in adult mice. Bone 18 33189914
2017 Progesterone-Induced miR-152 Inhibits the Proliferation of Endometrial Epithelial Cells by Downregulating WNT-1. Reproductive sciences (Thousand Oaks, Calif.) 18 28122483

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