Affinage

WNT11

Protein Wnt-11 · UniProt O96014

Length
354 aa
Mass
39.2 kDa
Annotated
2026-06-11
100 papers in source corpus 43 papers cited in narrative 43 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

WNT11 is a secreted, glycosylated, ECM-associated paracrine signaling protein that principally drives non-canonical Wnt cascades to coordinate cell polarity, collective cell movement, and tissue morphogenesis during development (PMID:8700530, PMID:10811221). During vertebrate gastrulation it controls convergent extension cell-non-autonomously through a divergent Dishevelled-dependent route that does not require canonical β-catenin signaling (PMID:10811221), signaling via Frizzled 7 to recruit and locally accumulate Dishevelled at cell contacts and adherens junctions together with the atypical cadherin Flamingo (PMID:17130287, PMID:17663724), and engaging the co-receptors Ryk (driving β-arrestin 2-dependent Dishevelled endocytosis) and Ror2 (PMID:18809723, PMID:24928507). Downstream, WNT11 converges on RhoA-Rho kinase (with Diaphanous), Rab5c-regulated E-cadherin endocytosis, and modulation of cadherin-based adhesion through Frizzled 7 adhesion-modulating complexes with PAPC and C-cadherin to tune cell cohesion and elongation (PMID:16019189, PMID:12062050, PMID:16198297, PMID:22908314). Beyond morphogenesis, WNT11 activates PKC, JNK, and Ca²⁺/CaMKII to direct cardiomyocyte and chondrocyte differentiation while suppressing β-catenin signaling, in heart development acting redundantly with Wnt5a and antagonizing canonical Wnt through caspase-dependent degradation of AKT/β-catenin to promote second heart field progenitors (PMID:12167861, PMID:15084607, PMID:16754689, PMID:25482987, PMID:22569553, PMID:25813538). In the kidney WNT11 sustains a positive autoregulatory feedback loop with GDNF/RET to pattern ureteric branching and additionally directs nephron progenitor polarity and stable attachment to branch tips (PMID:12783789, PMID:30651543, PMID:30516471). Context-dependently, WNT11 can also activate canonical Wnt/β-catenin signaling—maternal Wnt11 specifies the dorsal axis through EXT1/FRL1 and LRP6-mediated Axin degradation, and TPST-1-mediated tyrosine O-sulfation enables Wnt11/Wnt5a complexes with enhanced canonical activity (PMID:15797385, PMID:17202189, PMID:19747829). WNT11 secretion is itself spatially regulated: it is apically secreted in polarized epithelia via Asn40 glycan processing and galectin-3 (PMID:23613470), and its expression is driven by HIF-1α, ERG, ERRα/β-catenin, and Notch1 in cancer contexts where it promotes migration, invasion, amoeboid metastasis, and immune evasion (PMID:26861754, PMID:21242973, PMID:20870744, PMID:33082334, PMID:39920102).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 Medium

    Established that WNT11 is a bona fide secreted Wnt with paracrine signaling capacity, framing it as a diffusible morphogen rather than a purely cell-intrinsic factor.

    Evidence Conditioned-medium secretion assay, ECM fractionation, and co-culture transformation of mammary epithelial cells by Wnt11-expressing fibroblasts

    PMID:8700530

    Open questions at the time
    • No receptor or downstream pathway identified at this stage
    • Transformation readout does not define physiological signaling output
  2. 2000 High

    Resolved that WNT11 acts through a non-canonical, Dishevelled-dependent cascade distinct from the canonical Wnt pathway by showing convergent extension rescue with a canonical-deficient Dishevelled.

    Evidence Zebrafish silberblick loss-of-function genetics with dominant-negative Dishevelled rescue

    PMID:10811221

    Open questions at the time
    • Receptor not identified
    • Intracellular effectors downstream of Dishevelled not defined
  3. 2002 High

    Defined the intracellular effector logic of non-canonical WNT11 signaling, linking it to PKC/JNK in cardiogenesis and to Rho kinase in convergent extension cell elongation.

    Evidence Xenopus and P19 cell loss/gain-of-function with PKC/JNK inhibitors; dominant-negative Rok2 and epistatic suppression of slb/wnt11 in zebrafish

    PMID:12062050 PMID:12167861

    Open questions at the time
    • How a single ligand routes to distinct effectors in different tissues unresolved
    • Receptor coupling to PKC/JNK/Rok2 not mapped
  4. 2003 High

    Showed WNT11 operates within a reciprocal feedback loop with GDNF/RET to control kidney ureteric branching, establishing it as a node in a self-reinforcing morphogenetic circuit.

    Evidence Wnt11 null and Wnt11;Ret compound mutant mice with Gdnf in situ hybridization

    PMID:12783789

    Open questions at the time
    • Receptor mediating Wnt11 in kidney not identified
    • Mechanism by which Wnt11 maintains Gdnf expression not defined
  5. 2004 High

    Demonstrated WNT11 actively represses canonical Wnt signaling via receptor competition and intracellular Ca²⁺, and engages PKC/CaMKII to drive epithelial proliferation, clarifying its antagonistic relationship to β-catenin signaling.

    Evidence LEF-1 reporter, co-culture competition, Ca²⁺ manipulation, siRNA in P19; PKC/CaMKII assays in IEC6 cells

    PMID:15067007 PMID:15084607

    Open questions at the time
    • Selectivity of receptor competition mechanistically unexplained
    • Direct Ca²⁺ source not identified
  6. 2005 High

    Revealed a context-dependent canonical arm: maternal WNT11 can specify dorsal axis through EXT1 and the EGF-CFC protein FRL1, and morphogenesis is executed through Rab5c-dependent E-cadherin endocytosis and RhoA effectors.

    Evidence Xenopus maternal depletion of Wnt11/EXT1/FRL1 with FRL1 Co-IP; zebrafish Rab5c phenocopy/rescue and E-cadherin endocytosis; rhoA rescue of wnt11 mutants

    PMID:15797385 PMID:16019189 PMID:16198297

    Open questions at the time
    • How the same ligand selects canonical versus non-canonical output remains unresolved
    • FRL1/EXT1 biochemical role in receptor activation not defined
  7. 2006 High

    Provided a cell-biological mechanism for non-canonical signaling by showing WNT11 locally accumulates Frizzled 7 at contacts, recruiting Dishevelled and Flamingo to stabilize cell contacts independently of RhoA/Rok2.

    Evidence Live imaging, subcellular localization, and Co-IP of Wnt11/Frizzled7/Flamingo in zebrafish

    PMID:17130287

    Open questions at the time
    • Link between local Fz7/Dvl clustering and downstream transcription/cytoskeleton not fully mapped
  8. 2008 High

    Identified Ryk as a co-receptor enabling β-arrestin 2-dependent Dishevelled endocytosis required for WNT11 convergent extension, and established WNT11 as a directional PCP cue acting downstream of canonical Wnt in myogenesis.

    Evidence Ryk/Wnt11/β-arrestin 2 Co-IP and endocytosis assays in Xenopus; siRNA and ectopic-source PCP experiments in chick somites

    PMID:18809723 PMID:18987628

    Open questions at the time
    • Stoichiometry of Fz7/Ryk receptor complex unknown
    • How directional information is read out by myocytes not defined
  9. 2009 High

    Showed post-translational tyrosine O-sulfation by TPST-1 controls WNT11/Wnt5a complex formation that enhances canonical signaling, and that WNT11 promotes osteoblast maturation via β-catenin-dependent Rspo2 induction.

    Evidence Co-IP, sulfation-site mutagenesis, and reporter assays across oocyte/L-cell/hESC systems; Rspo2 knockdown and dominant-negative TCF in pre-osteoblasts

    PMID:19213727 PMID:19747829

    Open questions at the time
    • Physiological contexts where Wnt11/Wnt5a heterocomplexes form in vivo not established
    • Receptor for the sulfated complex not identified
  10. 2010 High

    Connected non-canonical WNT11 to physiological cardiac patterning and electrophysiology and to caspase-dependent suppression of β-catenin during cardiomyocyte differentiation, while extending its role to cancer cell survival and migration.

    Evidence Zebrafish optical mapping with L-type Ca²⁺ channel pharmacology; caspase-inhibitor and β-catenin assays; Wnt11 KO mouse N-cadherin/β-catenin patterning; PKA-dependent prostate cancer assays; ERRα/β-catenin/LEF-1 Co-IP

    PMID:19622544 PMID:20219091 PMID:20657579 PMID:20870744 PMID:21041481

    Open questions at the time
    • Mechanistic link between caspase activation and β-catenin/AKT turnover incomplete
    • How Wnt11 patterns N-cadherin/β-catenin at junctions not defined
  11. 2012 High

    Defined a molecular mechanism for adhesion control during convergent extension via two distinct Frizzled 7 adhesion-modulating complexes and established WNT11 as a co-required factor for second heart field development.

    Evidence Co-IP, domain mapping, endocytosis and cell-sorting assays in Xenopus; Wnt5a;Wnt11 compound KO mice with β-catenin reporters and ES cell differentiation

    PMID:17663724 PMID:22569553 PMID:22908314

    Open questions at the time
    • In vivo contribution of each adhesion complex not quantified
    • Redundancy boundaries between Wnt11 and Wnt5a not fully mapped
  12. 2014 High

    Identified Ror2 as a direct WNT11 receptor coupling to Dishevelled/RhoA in convergent extension, and showed WNT11/Wnt5a suppress β-catenin and promote heart field progenitors through caspase-dependent AKT degradation.

    Evidence Ror2/Wnt11 Co-IP, Ror2 site-directed mutagenesis, epistasis and transplantation in zebrafish; caspase and AKT assays in ES cells and mice

    PMID:24928507 PMID:25482987

    Open questions at the time
    • How Ror2, Fz7, and Ryk are partitioned across contexts unresolved
    • Caspase target specificity for AKT versus β-catenin not defined
  13. 2015 High

    Established redundant WNT11/Wnt5a control of body axis elongation via PCP-driven notochord convergent extension and p38-dependent EMT, and connected WNT11 to RhoA-mediated anoikis resistance in cancer.

    Evidence Wnt5a;Wnt11 compound KO mice with p38 phosphorylation and epithelial-marker analysis; p120/Kaiso regulation and RhoA activity in breast cancer cells

    PMID:25713299 PMID:25813538

    Open questions at the time
    • Receptor mediating p38 activation not identified
    • Generalizability of anoikis mechanism across tumor types untested
  14. 2018 High

    Identified FZD8 as a major WNT11 receptor in prostate cancer that couples to ATF2 transcription and forms a TGF-β-regulated receptor complex, and clarified WNT11's role in nephron progenitor polarity and attachment.

    Evidence Reciprocal Co-IP, domain mapping, FZD8 shRNA, ATF2 reporter in prostate cancer; Wnt11 KO mouse live imaging, polarity markers, RNA-seq, nephron counting

    PMID:29717114 PMID:30516471

    Open questions at the time
    • Mechanism of polarity control in kidney is post-transcriptional/signaling-level but undefined
    • How WNT11 integrates FZD8 with TGF-β receptors mechanistically unresolved
  15. 2020 Medium

    Defined a WNT11-FZD7-DAAM1-Rho-ROCK-Myosin II axis driving amoeboid invasion and metastasis, extending the morphogenetic cytoskeletal program to malignant dissemination.

    Evidence Knockdown of WNT11/FZD7/DAAM1, Rho-ROCK inhibitors, Myosin II assays, in vivo metastasis models in melanoma

    PMID:33082334

    Open questions at the time
    • Single-lab pathway model
    • Relative contribution of DAAM1 versus other Rho activators not quantified
  16. 2025 Medium

    Connected WNT11/CAMKII signaling to tumor immune evasion, showing it suppresses CD8+ T-cell recruitment and polarizes immunosuppressive macrophages, and that CAMKII inhibition sensitizes tumors to anti-PD-1.

    Evidence WNT11 overexpression, CAMKII inhibition, cytokine and T-cell assays, in vivo liver metastasis model with anti-PD-1

    PMID:39920102

    Open questions at the time
    • Single-lab study
    • Receptor mediating WNT11/CAMKII in this context not identified
    • Translatability of CAMKII inhibition to patients untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single secreted WNT11 ligand selects between canonical and non-canonical outputs and among distinct receptors (Frizzled 7, Frizzled 8, Frizzled 5, Ror2, Ryk) and effectors (PKC, JNK, RhoA/ROCK, CaMKII, caspase/AKT) in a tissue- and context-specific manner.
  • No unified model of receptor selection
  • Structural basis for ligand-receptor specificity unknown
  • Quantitative rules linking ligand dose/modification to pathway choice undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 6 GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005576 extracellular region 1 GO:0031012 extracellular matrix 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 4
Partners
FRL1FZD5FZD7FZD8ROR2RYKWNT5A
Complex memberships
Frizzled7 adhesion-modulating complexes (with PAPC and C-cadherin)WNT11-FZD7-DAAM1 complexWNT11-Frizzled7-Flamingo complexWnt11/Wnt5a sulfated complex

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Zebrafish Wnt11 (silberblick locus) mediates convergent extension movements during gastrulation in a cell non-autonomous manner; its phenotype is rescued by a truncated Dishevelled that does not signal through the canonical Wnt pathway, indicating Wnt11 acts through a divergent (non-canonical) signal transduction cascade. Genetic mapping, loss-of-function mutant analysis, rescue with dominant-negative Dishevelled construct Nature High 10811221
2002 Wnt11 is required for heart formation in Xenopus; it mediates cardiogenesis via non-canonical Wnt signaling that is independent of β-catenin and involves protein kinase C (PKC) and Jun N-terminal kinase (JNK). Loss- and gain-of-function experiments in Xenopus; conditioned medium treatment of P19 mouse embryonic carcinoma cells; pathway inhibitor assays for PKC and JNK Nature High 12167861
2005 Maternal Wnt11 activates the canonical Wnt signaling pathway to specify the dorsal axis in Xenopus; this activation requires the glycosyl transferase EXT1 and the EGF-CFC protein FRL1, which interacts with Wnt11. Loss-of-function (depletion of maternal Wnt11, EXT1, FRL1 by antisense oligonucleotides); co-immunoprecipitation of FRL1 with Wnt11 Cell High 15797385
2003 Wnt11 and Ret/GDNF cooperate in a positive autoregulatory feedback loop during kidney development: Wnt11 maintains GDNF expression in the mesenchyme, and GDNF/Ret signaling maintains Wnt11 expression in ureteric tips; loss of Wnt11 reduces GDNF, and Wnt11/Ret double mutants show synergistic ureteric branching defects. Targeted gene knockout (Wnt11 null mice), genetic epistasis (Wnt11;Ret compound mutants), in situ hybridization for Gdnf expression Development High 12783789
2002 Rho kinase 2 (Rok2) acts downstream of Wnt11 to mediate mediolateral cell elongation required for convergent extension movements in zebrafish; overexpression of Rok2 partially suppresses the slb/wnt11 gastrulation phenotype, and ectopic non-canonical Wnts modulate Rok2 intracellular distribution. Dominant-negative Rok2 overexpression, genetic suppression of slb/wnt11 mutant phenotype by Rok2 overexpression, transplantation experiments Current Biology High 12062050
2005 Wnt11 controls tissue morphogenesis during zebrafish gastrulation by regulating E-cadherin-mediated cell cohesion via the GTPase Rab5c, a regulator of early endocytosis; blocking Rab5c phenocopies slb/wnt11 mutants, and enhancing Rab5c in slb/wnt11 mutants rescues the phenotype. Loss-of-function, rescue experiments, epistasis in zebrafish embryos; E-cadherin endocytosis assays Developmental Cell High 16198297
2006 Wnt11 locally accumulates its receptor Frizzled 7 at cell contact sites in zebrafish embryonic cells; Frizzled 7 accumulations in turn recruit Dishevelled and Wnt11 itself, increasing local cell contact persistence through interaction with the atypical cadherin Flamingo, without requiring RhoA or Rok2 activity. Live imaging, subcellular localization studies, co-immunoprecipitation, dominant-negative and overexpression experiments in zebrafish Journal of Cell Biology High 17130287
2008 Ryk cooperates with Frizzled 7 to mediate Wnt11-stimulated β-arrestin 2-dependent endocytosis of Dishevelled, which is required for non-canonical Wnt11 signaling in convergent extension movements in Xenopus. Co-immunoprecipitation (Ryk with Wnt11 and β-arrestin 2), morpholino knockdown, endocytosis assays in Xenopus dorsal marginal zone Journal of Cell Biology High 18809723
2008 WNT11 acts as a directional cue for oriented myocyte elongation in chick somites through the planar cell polarity (PCP) pathway; a localized ectopic source of WNT11 changes myocyte orientation, operating downstream of the WNT/β-catenin pathway that initiates the myogenic program. Loss-of-function (siRNA in somites), ectopic WNT11 source placement, epistasis with WNT/β-catenin pathway in chick embryos Nature High 18987628
2004 Wnt11 represses canonical Wnt signaling through multiple mechanisms: (1) receptor competition (preventing Wnt1/Wnt3/Wnt3a but not Wnt7a/7b from activating LEF-1), and (2) elevation of intracellular Ca²⁺ that inhibits canonical signaling; siRNA knockdown of endogenous Wnt11 in P19 cells increases LEF-1 reporter activity. LEF-1 reporter assays in NIH3T3 and P19 cells, co-culture competition experiments, siRNA knockdown, intracellular Ca²⁺ manipulation Journal of Biological Chemistry High 15067007
2005 In zebrafish, Wnt11 and Frizzled 5 promote eye field development partly through local antagonism of Wnt/β-catenin signaling and additionally regulate the cohesion of eye field cells. Loss-of-function and epistasis experiments in zebrafish embryos; cell cohesion assays Neuron Medium 15996547
2005 RhoA acts downstream of Wnt11 (and Wnt5) to regulate convergent extension movements in zebrafish, exerting its effects via two effectors: Rho kinase and Diaphanous (mDia); rhoA mRNA rescues CE defects in wnt11 mutants. Morpholino knockdown of rhoA in zebrafish, rescue of wnt11 mutants with rhoA mRNA, ectopic expression of Rho kinase and Diaphanous Cellular Signalling Medium 16019189
2007 Wnt11 canonical signaling in Xenopus oocytes and early embryos operates through LRP6-mediated degradation of Axin: in the oocyte Wnt11/LRP6 maintains low β-catenin by regulating Axin, while in the embryo asymmetric Wnt11/LRP6 stabilizes β-catenin on the dorsal side. Morpholino depletion of LRP6 and Wnt11 in Xenopus oocytes/embryos; Axin protein level assays; β-catenin localization Development Medium 17202189
2009 Wnt11/5a complexes, formed through TPST-1-mediated O-sulfation of specific tyrosine residues on Wnt11, have greater canonical Wnt signaling activity than either Wnt11 or Wnt5a alone; sulfation of Wnt11 is required for its interaction with Wnt5a. Co-immunoprecipitation of Wnt11/Wnt5a; canonical signaling reporter assays in Xenopus oocytes, mouse L cells, and human ESCs; TPST-1 loss-of-function; mutagenesis of sulfation sites Current Biology High 19747829
2009 Wnt11 promotes osteoblast maturation and mineralization through β-catenin-dependent induction of R-spondin 2 (Rspo2); knockdown of Rspo2 abrogates Wnt11-mediated osteoblast maturation, and dominant-negative TCF blocks Wnt11-mediated Rspo2 expression. Overexpression and knockdown (siRNA of Rspo2) in MC3T3E1 pre-osteoblasts; dominant-negative TCF; alkaline phosphatase and mineralization assays Journal of Biological Chemistry Medium 19213727
2008 Sfrp5 locally inhibits Wnt11 to coordinate canonical (Wnt/β-catenin) and non-canonical (Wnt/PCP) signaling in Xenopus foregut development: depletion of Sfrp5 leads to inappropriate Wnt11-mediated β-catenin and PCP signaling causing cell fate and epithelial adhesion defects, respectively. Morpholino depletion of Sfrp5 and Wnt11 in Xenopus; reporter assays for β-catenin and PCP signaling; rescue experiments Genes & Development Medium 18981481
2010 Non-canonical Wnt11 signaling in the zebrafish heart establishes a myocardial electrical gradient through effects on transmembrane Ca²⁺ conductance mediated by the L-type calcium channel; the traditional planar cell polarity pathway is not involved. High-speed optical mapping of transmembrane potentials and Ca²⁺ in zebrafish heart; loss-of-function of Wnt11; pharmacological manipulation of L-type calcium channel Nature High 20657579
2010 Wnt11 promotes neuroendocrine-like differentiation and survival of prostate cancer cells via cyclic AMP-dependent protein kinase; silencing Wnt11 causes apoptosis in androgen-depleted LNCaP and PC3 cells; Wnt11 also promotes cell migration/invasion. Ectopic Wnt11 expression, siRNA knockdown, PKA inhibitor treatment, migration/invasion assays in prostate cancer cell lines Molecular Cancer Medium 20219091
2010 ERRα and β-catenin form a macromolecular complex with LEF-1 in cells and co-operatively induce WNT11 transcription; WNT11 then acts in an autocrine manner to increase cancer cell migration; WNT11-neutralizing antibodies abrogate the ERRα/β-catenin promigratory effect. Co-immunoprecipitation of ERRα/β-catenin/LEF-1; WNT11 conditioned medium; WNT11 neutralizing antibodies; siRNA knockdown; migration assays Cancer Research Medium 20870744
2010 Wnt11 promotes cardiomyocyte differentiation while suppressing β-catenin stabilization through activation of a caspase 3 signaling cascade; inhibition of caspase activity leads to β-catenin accumulation and reduced myocyte differentiation. Wnt11 stimulation of cardiomyocyte cultures, caspase inhibitor treatment, β-catenin western blot, differentiation assays Molecular and Cellular Biology Medium 21041481
2014 Wnt5a and Wnt11 inhibit canonical Wnt/β-catenin signaling and promote second heart field progenitor development through Caspase-dependent degradation of AKT; Caspase inhibition blocked Wnt5a/Wnt11-induced suppression of both phosphorylated and total Akt, and Akt inhibition alone was sufficient to promote second heart field markers. Caspase activity assays, AKT western blot, Caspase inhibitor treatment in differentiating ES cells and in vivo (mouse), SHF marker expression Developmental Biology Medium 25482987
2013 Wnt11 is secreted apically in polarized epithelial cells via a mechanism requiring complex/hybrid glycan processing at Asn40 and galectin-3, distinct from the basolateral Wntless (Wls)-dependent pathway used by Wnt3a; fusion of the Asn40 glycosylation site of Wnt11 onto Wnt3a redirected Wnt3a to apical secretion. Mass-spectrometric glycan analysis of Wnt11, mutational analysis of glycosylation sites, apical/basolateral secretion assays in polarized MDCK cells, galectin-3 knockdown Journal of Cell Science High 23613470
2012 Wnt11/Frizzled 7 controls cell adhesion during convergent extension by forming two separate adhesion-modulating complexes (AMCs): one with PAPC (AMCP) that blocks PAPC internalization, preventing C-cadherin clustering, and one with C-cadherin (AMCC) that competes with C-cadherin cis-dimerization; both act in parallel to reduce cell adhesion. Co-immunoprecipitation, domain mapping of Fz7 interactions, endocytosis (dynamin1/clathrin-dependent) assays, cell sorting assays in Xenopus Journal of Cell Biology High 22908314
2007 Wnt11 stimulation induces polarized accumulation of Dishevelled at apical adherens junctions in Xenopus via Frizzled 7; the DIX domain of Dishevelled is required for its translocation in response to Wnt11; Frizzled 7 itself accumulates at adherens junctions in response to Wnt11. Morpholino knockdown of Frizzled 7, Dishevelled localization imaging, domain deletion analysis (DIX domain), Wnt11 stimulation assays in Xenopus ectodermal explants Genes to Cells Medium 17663724
2004 Wnt11 stimulates proliferation, migration, and contact-independent growth of IEC6 intestinal epithelial cells via a β-catenin-independent mechanism involving PKC and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII); PKC inhibition reduces Wnt11-induced foci formation; Wnt11 also redistributes E-cadherin. Conditioned medium treatment and stable transfection with Wnt11; PKC activity assays; CaMKII activity assays; PKC inhibitor; E-cadherin immunofluorescence; foci formation assays Journal of Biological Chemistry Medium 15084607
2006 Wnt11 (via non-canonical pathway) activates PKC to stimulate type II collagen expression in chondrocytes; a PKC inhibitor blocks this effect; in contrast, Wnt-5a activates JNK to inhibit type II collagen expression. Conditioned medium from Wnt-11 or Wnt-5a expressing cells, PKC and JNK inhibitors, siRNA knockdown, collagen expression assays Journal of Biological Chemistry Medium 16754689
2008 Noncanonical Wnt11 signaling induces cardiomyogenic differentiation of adult bone marrow mononuclear cells via PKC and JNK pathways; Wnt11-induced cardiac gene expression is abolished by PKC inhibitor bisindolylmaleimide I and partially by JNK inhibitor SP600125. Wnt11 conditioned medium treatment of BMMNCs, PKC and JNK pharmacological inhibitors, cardiac marker qRT-PCR and immunocytochemistry Circulation Medium 18427129
2014 Ror2 physically interacts with Wnt11 and functions as a receptor mediating Wnt11 signaling during convergent extension in zebrafish; Tyr-647 and Ser-863 of Ror2 are essential for mediating Wnt11 action; Dishevelled and RhoA act downstream of Wnt11-Ror2. Co-immunoprecipitation of Ror2 and Wnt11, dominant-negative Ror2 overexpression, epistasis with wnt11 morpholino, site-directed mutagenesis of Ror2, transplantation experiments in zebrafish Journal of Biological Chemistry High 24928507
2018 FZD8 is a major Wnt-11 receptor in prostate cancer; FZD8 co-localizes and co-immunoprecipitates with Wnt-11, potentiates Wnt-11 activation of ATF2-dependent transcription, and forms a TGF-β-regulated complex with TGF-β receptors mediated by the extracellular domains of FZD8 and TGFBR1. Co-immunoprecipitation, co-localization, FZD8 silencing (shRNA), ATF2 reporter assay, 3D organotypic assays, EMT gene expression analysis in prostate cancer cell lines Nature Communications High 29717114
2015 Wnt11 and Wnt5a play redundant roles in mouse anterior-posterior axis elongation by regulating convergent extension of notochord cells via the PCP pathway and by promoting EMT through induction of p38 (Mapk14) phosphorylation; compound Wnt5a;Wnt11 mutants show ectopic accumulation of mesodermal precursors with epithelial markers in the primitive streak. Wnt5a;Wnt11 compound mouse knockout, p38 phosphorylation assays, epithelial marker expression, notochord CE analysis Development High 25813538
2010 Wnt-11 controls ventricular myocardium organization by patterning N-cadherin and β-catenin expression; in Wnt-11 knockout mice, coordinated organization, intercellular contacts, and cytoskeleton of differentiating ventricular cardiomyocytes are disrupted, leading to thinner ventricular wall and reduced Gata-4, Nkx2.5, Mef2c expression. Wnt11 knockout mouse, N-cadherin/β-catenin localization immunostaining, cardiac functional assessment (echocardiography), gene expression analysis Cardiovascular Research Medium 19622544
2012 Wnt5a and Wnt11 are co-required for second heart field development in mice; their loss leads to increased Wnt/β-catenin signaling, and ectopic Wnt5a/Wnt11 inhibits β-catenin signaling and promotes cardiac progenitor development in ES cells. Wnt5a;Wnt11 compound mouse knockout, β-catenin reporter assays, ES cell differentiation, Islet1 marker analysis Development High 22569553
2020 WNT11-FZD7-DAAM1 signaling activates Rho-ROCK1/2-Myosin II to regulate tumour-initiating potential, amoeboid invasion, and distant metastasis in melanoma. Loss-of-function (knockdown of WNT11, FZD7, DAAM1), Rho-ROCK inhibitors, Myosin II activity assays, in vivo metastasis models Nature Communications Medium 33082334
1996 Murine Wnt11 encodes a secreted glycoprotein that becomes associated with the extracellular matrix; Wnt11-expressing Rat2 fibroblasts induce morphological transformation of adjacent C57MG mammary epithelial cells in co-culture, demonstrating paracrine signaling activity. Conditioned medium secretion assay, extracellular matrix fractionation, co-culture transformation assay Oncogene Medium 8700530
1999 Cytoplasmic rotation in Xenopus embryos triggers differential cytoplasmic polyadenylation of maternal Xwnt-11 mRNA along the dorsal-ventral axis, resulting in asymmetric accumulation of Wnt11 protein on the dorsal side through translational regulation. Polyadenylation assays, immunodetection of Wnt11 protein, microtubule disruption experiments in Xenopus embryos Developmental Biology Medium 10525335
2016 WNT11 transcription is induced by hypoxia primarily through HIF-1α binding to hypoxia response elements (HREs) in the WNT11 promoter; WNT11 stimulates proliferation, migration, and invasion and increases MMP-2 and MMP-9 activity. HIF-1α loss-of-function, HRE reporter assays, gain-of-function and loss-of-function of WNT11, MMP activity assays in multiple cancer cell types Scientific Reports Medium 26861754
2011 WNT11 is a direct transcriptional target of the ETS transcription factor ERG; ERG occupies the WNT11 chromatin locus (ChIP-chip), ERG knockdown reduces WNT11 transcripts, and ERG induction promotes morphological transformation through WNT11 signals. ChIP-chip genome-wide screen, ChIP validation in patient samples, siRNA knockdown of ERG, tet-on ERG induction, WNT11 siRNA rescue Oncogene Medium 21242973
2015 Nuclear p120-catenin relieves Kaiso-mediated transcriptional repression of Wnt11 in anchorage-independent lobular breast cancer cells, and Wnt11 in turn promotes RhoA activation to confer anoikis resistance. Genome-wide mRNA profiling, Kaiso/p120 knockdown and overexpression, RhoA activity assay, anoikis resistance assay in mouse ILC cells Disease Models & Mechanisms Medium 25713299
2016 WNT-11 cooperates with TGF-β1 to drive smooth muscle α-actin (sm-α-actin) expression in airway smooth muscle cells via a RhoA-Rho kinase-actin cytoskeleton-MRTF-A signaling axis; WNT-11 knockdown attenuates TGF-β1-induced MRTF-A nuclear translocation and sm-α-actin expression. WNT-11 siRNA knockdown, Rho kinase inhibitor (Y27632), actin polymerization inhibitor (latrunculin A), MRTF-A nuclear localization imaging, sm-α-actin expression assays American Journal of Physiology – Lung Cellular and Molecular Physiology Medium 27422998
2018 Wnt11 directs nephron progenitor polarity and stable attachment to ureteric branch tips in the kidney; in Wnt11 mutants, progenitors lose polarized marker distribution and stably detach/reattach from tips, accelerating differentiation and halving nephron endowment; RNA-seq showed no significant differences in gene expression, suggesting a post-transcriptional or signaling-level mechanism. Wnt11 knockout mouse, live imaging of nephron progenitors, polarity marker immunostaining, RNA-seq, nephron counting eLife Medium 30516471
2019 A positive feedback loop between WNT11 and GDNF permits dense packing of ureteric tips in kidney branching morphogenesis, as confirmed experimentally in cultured wildtype and mutant ureteric buds following computational prediction. Image-based computational modeling, experimental validation in cultured kidney explants, WNT11 and GDNF expression analysis Nature Communications Medium 30651543
2012 Notch1 activation inhibits fibroblast growth through a Wnt11-dependent induction of WISP-1/CCN4; blocking Wnt11 expression reduces WISP-1 levels and abrogates Notch-induced growth inhibition; this pathway is Wnt1-independent. Notch1 knockout MEFs, NICD1 overexpression, siRNA knockdown of WISP-1 and Wnt11, cell growth assays PLoS ONE Medium 22715413
2025 WNT11 promotes CD8+ T-cell exclusion in liver metastasis by decreasing CXCL10 and CCL4 expression through CAMKII-mediated β-catenin/AFF3 downregulation; WNT11 also induces IL17D expression via CAMKII/NF-κB to polarize immunosuppressive macrophages that suppress CD8+ T cells; CAMKII inhibition increases anti-PD-1 therapy efficacy. WNT11 overexpression in tumor cells, CAMKII inhibition, T-cell recruitment and activity assays, cytokine expression analysis, in vivo liver metastasis mouse model with anti-PD-1 treatment Nature Communications Medium 39920102

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. Nature 861 10811221
2002 Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis. Nature 430 12167861
2005 Maternal wnt11 activates the canonical wnt signaling pathway required for axis formation in Xenopus embryos. Cell 410 15797385
2003 Wnt11 and Ret/Gdnf pathways cooperate in regulating ureteric branching during metanephric kidney development. Development (Cambridge, England) 359 12783789
2009 Microwell-mediated control of embryoid body size regulates embryonic stem cell fate via differential expression of WNT5a and WNT11. Proceedings of the National Academy of Sciences of the United States of America 292 19805103
2002 Zebrafish Rho kinase 2 acts downstream of Wnt11 to mediate cell polarity and effective convergence and extension movements. Current biology : CB 279 12062050
1996 Proteoglycans are required for maintenance of Wnt-11 expression in the ureter tips. Development (Cambridge, England) 256 8951078
2005 Wnt11 functions in gastrulation by controlling cell cohesion through Rab5c and E-cadherin. Developmental cell 235 16198297
2005 Early stages of zebrafish eye formation require the coordinated activity of Wnt11, Fz5, and the Wnt/beta-catenin pathway. Neuron 163 15996547
2008 WNT11 acts as a directional cue to organize the elongation of early muscle fibres. Nature 161 18987628
2007 Reduction of BMP4 activity by gremlin 1 enables ureteric bud outgrowth and GDNF/WNT11 feedback signalling during kidney branching morphogenesis. Development (Cambridge, England) 151 17522159
1999 WNT11 promotes cardiac tissue formation of early mesoderm. Developmental dynamics : an official publication of the American Association of Anatomists 143 10474165
2010 Wnt-11 promotes neuroendocrine-like differentiation, survival and migration of prostate cancer cells. Molecular cancer 140 20219091
2003 Slb/Wnt11 controls hypoblast cell migration and morphogenesis at the onset of zebrafish gastrulation. Development (Cambridge, England) 134 13129848
2008 Sfrp5 coordinates foregut specification and morphogenesis by antagonizing both canonical and noncanonical Wnt11 signaling. Genes & development 133 18981481
1995 Murine Wnt-11 and Wnt-12 have temporally and spatially restricted expression patterns during embryonic development. Mechanisms of development 123 7547479
2010 WNT11 expression is induced by estrogen-related receptor alpha and beta-catenin and acts in an autocrine manner to increase cancer cell migration. Cancer research 121 20870744
2010 Wnt11 patterns a myocardial electrical gradient through regulation of the L-type Ca(2+) channel. Nature 116 20657579
2012 Wnt5a and Wnt11 are essential for second heart field progenitor development. Development (Cambridge, England) 115 22569553
2004 Multiple mechanisms for Wnt11-mediated repression of the canonical Wnt signaling pathway. The Journal of biological chemistry 115 15067007
2001 Molecular cloning and characterization of human WNT11. International journal of molecular medicine 112 11712081
2006 Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane. The Journal of cell biology 105 17130287
2009 Wnt11 promotes osteoblast maturation and mineralization through R-spondin 2. The Journal of biological chemistry 103 19213727
2004 Wnt11 facilitates embryonic stem cell differentiation to Nkx2.5-positive cardiomyocytes. Biochemical and biophysical research communications 102 15541384
2005 RhoA acts downstream of Wnt5 and Wnt11 to regulate convergence and extension movements by involving effectors Rho kinase and Diaphanous: use of zebrafish as an in vivo model for GTPase signaling. Cellular signalling 101 16019189
1998 Isolation, characterisation and embryonic expression of WNT11, a gene which maps to 11q13.5 and has possible roles in the development of skeleton, kidney and lung. Gene 101 9757009
1997 Wnt-11 is expressed in early avian mesoderm and required for the differentiation of the quail mesoderm cell line QCE-6. Development (Cambridge, England) 99 9053328
2006 Opposing roles of WNT-5A and WNT-11 in interleukin-1beta regulation of type II collagen expression in articular chondrocytes. The Journal of biological chemistry 98 16754689
2006 wnt3a but not wnt11 supports self-renewal of embryonic stem cells. Biochemical and biophysical research communications 95 16707109
2018 Frizzled-8 integrates Wnt-11 and transforming growth factor-β signaling in prostate cancer. Nature communications 93 29717114
2008 Ryk cooperates with Frizzled 7 to promote Wnt11-mediated endocytosis and is essential for Xenopus laevis convergent extension movements. The Journal of cell biology 93 18809723
2005 Wnt11-R, a protein closely related to mammalian Wnt11, is required for heart morphogenesis in Xenopus. Developmental biology 93 15708567
2004 Wnt11 signaling promotes proliferation, transformation, and migration of IEC6 intestinal epithelial cells. The Journal of biological chemistry 90 15084607
2017 3,3'-Diindolylmethane stimulates exosomal Wnt11 autocrine signaling in human umbilical cord mesenchymal stem cells to enhance wound healing. Theranostics 88 28529644
2015 Wnt5a and Wnt11 regulate mammalian anterior-posterior axis elongation. Development (Cambridge, England) 85 25813538
2004 Sprouty proteins regulate ureteric branching by coordinating reciprocal epithelial Wnt11, mesenchymal Gdnf and stromal Fgf7 signalling during kidney development. Development (Cambridge, England) 85 15201220
2007 Wnt11/beta-catenin signaling in both oocytes and early embryos acts through LRP6-mediated regulation of axin. Development (Cambridge, England) 80 17202189
1998 Zebrafish wnt11: pattern and regulation of the expression by the yolk cell and No tail activity. Mechanisms of development 77 9507106
2020 WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion. Nature communications 73 33082334
2015 MiR-154-5p regulates osteogenic differentiation of adipose-derived mesenchymal stem cells under tensile stress through the Wnt/PCP pathway by targeting Wnt11. Bone 71 25959411
2014 Wnt5a and Wnt11 inhibit the canonical Wnt pathway and promote cardiac progenitor development via the Caspase-dependent degradation of AKT. Developmental biology 67 25482987
2011 Wnt11 in 2011 - the regulation and function of a non-canonical Wnt. Acta physiologica (Oxford, England) 65 21447091
2010 Wnt-11 signalling controls ventricular myocardium development by patterning N-cadherin and beta-catenin expression. Cardiovascular research 64 19622544
2008 Non-canonical Wnt signaling through Wnt5a/b and a novel Wnt11 gene, Wnt11b, regulates cell migration during avian gastrulation. Developmental biology 64 18602094
2010 Wnt11 promotes cardiomyocyte development by caspase-mediated suppression of canonical Wnt signals. Molecular and cellular biology 63 21041481
2019 Image-based modeling of kidney branching morphogenesis reveals GDNF-RET based Turing-type mechanism and pattern-modulating WNT11 feedback. Nature communications 61 30651543
2009 Wnt11/5a complex formation caused by tyrosine sulfation increases canonical signaling activity. Current biology : CB 60 19747829
2013 The apical and basolateral secretion of Wnt11 and Wnt3a in polarized epithelial cells is regulated by different mechanisms. Journal of cell science 59 23613470
2010 Noncanonical Wnt11 inhibits hepatocellular carcinoma cell proliferation and migration. Molecular cancer research : MCR 59 20103596
1999 Spatially regulated translation in embryos: asymmetric expression of maternal Wnt-11 along the dorsal-ventral axis in Xenopus. Developmental biology 59 10525335
2024 Mechanical stiffness promotes skin fibrosis via Piezo1-Wnt2/Wnt11-CCL24 positive feedback loop. Cell death & disease 58 38267432
2009 GLI3 repressor controls nephron number via regulation of Wnt11 and Ret in ureteric tip cells. PloS one 58 19809516
2008 Noncanonical Wnt11 signaling is sufficient to induce cardiomyogenic differentiation in unfractionated bone marrow mononuclear cells. Circulation 57 18427129
2019 Regulation of WNT5A and WNT11 during MSC in vitro chondrogenesis: WNT inhibition lowers BMP and hedgehog activity, and reduces hypertrophy. Cellular and molecular life sciences : CMLS 54 30980110
2012 Wnt-11 and Fz7 reduce cell adhesion in convergent extension by sequestration of PAPC and C-cadherin. The Journal of cell biology 54 22908314
2018 Wnt11 directs nephron progenitor polarity and motile behavior ultimately determining nephron endowment. eLife 53 30516471
1995 A chicken Wnt gene, Wnt-11, is involved in dermal development. Biochemical and biophysical research communications 53 7779076
2008 Noncanonical Wnt11 signaling and cardiomyogenic differentiation. Trends in cardiovascular medicine 50 19232955
2007 Wnt11/Fgfr1b cross-talk modulates the fate of cells in palate development. Developmental biology 50 18191119
2018 Secreted AGR2 promotes invasion of colorectal cancer cells via Wnt11-mediated non-canonical Wnt signaling. Experimental cell research 49 29427622
2016 Induction of WNT11 by hypoxia and hypoxia-inducible factor-1α regulates cell proliferation, migration and invasion. Scientific reports 47 26861754
2011 Possible involvement of Wnt11 in colorectal cancer progression. Molecular carcinogenesis 47 22161723
2014 Overexpression of Wnt11 promotes chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in synergism with TGF-β. Molecular and cellular biochemistry 45 24474615
2011 Distinct roles for Wnt-4 and Wnt-11 during retinoic acid-induced neuronal differentiation. Stem cells (Dayton, Ohio) 45 21280163
2009 Zebrafish eaf1 and eaf2/u19 mediate effective convergence and extension movements through the maintenance of wnt11 and wnt5 expression. The Journal of biological chemistry 44 19380582
2006 Wnt11-R signaling regulates a calcium sensitive EMT event essential for dorsal fin development of Xenopus. Developmental biology 43 17240368
2011 Paracrine effect of Wnt11-overexpressing mesenchymal stem cells on ischemic injury. Stem cells and development 42 21463175
2014 Ror2 receptor mediates Wnt11 ligand signaling and affects convergence and extension movements in zebrafish. The Journal of biological chemistry 40 24928507
2011 Genome-wide screen reveals WNT11, a non-canonical WNT gene, as a direct target of ETS transcription factor ERG. Oncogene 38 21242973
2011 Wingless homolog Wnt11 suppresses bacterial invasion and inflammation in intestinal epithelial cells. American journal of physiology. Gastrointestinal and liver physiology 38 21903761
2019 Ascl1-induced Wnt11 regulates neuroendocrine differentiation, cell proliferation, and E-cadherin expression in small-cell lung cancer and Wnt11 regulates small-cell lung cancer biology. Laboratory investigation; a journal of technical methods and pathology 35 31231131
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2006 Regulation of ectodermal Wnt6 expression by the neural tube is transduced by dermomyotomal Wnt11: a mechanism of dermomyotomal lip sustainment. Development (Cambridge, England) 34 16818447
2015 Nuclear p120-catenin regulates the anoikis resistance of mouse lobular breast cancer cells through Kaiso-dependent Wnt11 expression. Disease models & mechanisms 33 25713299
2018 Long noncoding RNA ABHD11-AS1 promote cells proliferation and invasion of colorectal cancer via regulating the miR-1254-WNT11 pathway. Journal of cellular physiology 32 30537177
2011 Transduction of Wnt11 promotes mesenchymal stem cell transdifferentiation into cardiac phenotypes. Stem cells and development 32 21231807
2008 Wnt-11 signaling leads to down-regulation of the Wnt/beta-catenin, JNK/AP-1 and NF-kappaB pathways and promotes viability in the CHO-K1 cells. Experimental cell research 32 18572162
2003 Wnt11 and Wnt7a are up-regulated in association with differentiation of cardiac conduction cells in vitro and in vivo. Developmental dynamics : an official publication of the American Association of Anatomists 32 12889062
2020 Upregulated Wnt-11 and miR-21 Expression Trigger Epithelial Mesenchymal Transition in Aggressive Prostate Cancer Cells. Biology 31 32182839
2021 Cardiac Wnt5a and Wnt11 promote fibrosis by the crosstalk of FZD5 and EGFR signaling under pressure overload. Cell death & disease 30 34564708
2018 Wnt11 promotes BMP9-induced osteogenic differentiation through BMPs/Smads and p38 MAPK in mesenchymal stem cells. Journal of cellular biochemistry 30 30010216
2018 Role of Wnt11 during Osteogenic Differentiation of Human Mesenchymal Stem Cells on Microstructured Titanium Surfaces. Scientific reports 29 29872092
2018 Co-expression of Akt1 and Wnt11 promotes the proliferation and cardiac differentiation of mesenchymal stem cells and attenuates hypoxia/reoxygenation-induced cardiomyocyte apoptosis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 29 30243083
2016 Cooperative signaling by TGF-β1 and WNT-11 drives sm-α-actin expression in smooth muscle via Rho kinase-actin-MRTF-A signaling. American journal of physiology. Lung cellular and molecular physiology 28 27422998
1996 Murine WNT11 is a secreted glycoprotein that morphologically transforms mammary epithelial cells. Oncogene 26 8700530
2018 Downregulation of WNT11 is associated with bladder tissue fibrosis in patients with interstitial cystitis/bladder pain syndrome without Hunner lesion. Scientific reports 25 29955137
2013 Wnt11 expression in rat dental pulp and promotional effects of Wnt signaling on odontoblast differentiation. Congenital anomalies 25 23998262
2010 Negative regulation of wnt11 expression by Jnk signaling during zebrafish gastrulation. Journal of cellular biochemistry 25 20564202
2007 Wnt11 stimulation induces polarized accumulation of Dishevelled at apical adherens junctions through Frizzled7. Genes to cells : devoted to molecular & cellular mechanisms 25 17663724
2014 Mapping the dynamic expression of Wnt11 and the lineage contribution of Wnt11-expressing cells during early mouse development. Developmental biology 24 25448697
2017 Wnt11 regulates cardiac chamber development and disease during perinatal maturation. JCI insight 22 28878122
2012 Involvement of the WNT and FGF signaling pathways in non-isolated anorectal malformations: sequencing analysis of WNT3A, WNT5A, WNT11, DACT1, FGF10, FGFR2 and the T gene. International journal of molecular medicine 22 22961180
2025 WNT11 Promotes immune evasion and resistance to Anti-PD-1 therapy in liver metastasis. Nature communications 20 39920102
2019 Fibronectin regulates the self-renewal of rabbit limbal epithelial stem cells by stimulating the Wnt11/Fzd7/ROCK non-canonical Wnt pathway. Experimental eye research 20 31150636
2014 Clinical significance of Wnt-11 and squamous cell carcinoma antigen expression in cervical cancer. Medical oncology (Northwood, London, England) 20 24737009
2012 Inhibition of fibroblast growth by Notch1 signaling is mediated by induction of Wnt11-dependent WISP-1. PloS one 20 22715413
2017 Tissue specific requirements for WNT11 in developing outflow tract and dorsal mesenchymal protrusion. Developmental biology 19 28669819
2016 Wnt11 Gene Therapy with Adeno-associated Virus 9 Improves Recovery from Myocardial Infarction by Modulating the Inflammatory Response. Scientific reports 19 26882996
2016 Impairment of Wnt11 function leads to kidney tubular abnormalities and secondary glomerular cystogenesis. BMC developmental biology 19 27582005
2011 Lentivirus-mediated Wnt11 gene transfer enhances Cardiomyogenic differentiation of skeletal muscle-derived stem cells. Molecular therapy : the journal of the American Society of Gene Therapy 19 21304494

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