Affinage

WNT6

Protein Wnt-6 · UniProt Q9Y6F9

Length
365 aa
Mass
39.7 kDa
Annotated
2026-04-28
64 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

WNT6 is a secreted cysteine-rich glycoprotein that functions as a paracrine and autocrine ligand activating primarily canonical β-catenin–dependent signaling to regulate cell fate decisions across diverse developmental and adult tissue contexts. WNT6 signals through Frizzled receptors (FZD4, FZD7) to stabilize β-catenin, activate TCF/LEF transcription, and control mesenchymal stem cell fate by inhibiting adipogenesis and promoting osteoblastogenesis, while also driving kidney tubulogenesis (upstream of Wnt4), primitive endoderm epithelialization (via β-catenin–Snail1), uterine decidualization (via cyclin B1), and restriction of cardiomyogenesis (PMID:21872687, PMID:11948913, PMID:18160257, PMID:23175771, PMID:18804460). In macrophages, WNT6 promotes proliferation through a β-catenin-independent ERK–c-Myc axis and drives M2 polarization and foam cell formation via ACC2-dependent lipid accumulation, facilitating intracellular Mycobacterium tuberculosis survival (PMID:24123681, PMID:34255743). Context-dependent engagement of non-canonical pathways occurs in neural crest induction (chick ectoderm), dental pulp cell migration (JNK), and Drosophila niche maintenance (Rac1/Cdc42), and WNT6 transcription is directly regulated by GATA6, FOXA2, PLAGL2, and Caveolin-1/β-catenin (PMID:17685490, PMID:24935540, PMID:33582096, PMID:22607194, PMID:30535429, PMID:22370641).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2001 Medium

    Establishing the molecular identity of WNT6 as a secreted glycoprotein with a signal peptide and WNT domain, clustered with WNT10A on chromosome 2q35, provided the foundation for functional studies.

    Evidence Molecular cloning and sequence analysis of human WNT6 cDNA

    PMID:11350055

    Open questions at the time
    • No functional assays performed
    • Post-translational lipid modifications not characterized
    • Receptor specificity unknown
  2. 2002 High

    Demonstrating that Wnt6 induces kidney tubulogenesis and rescues Wnt4-mutant mesenchyme established WNT6 as a functional canonical Wnt ligand acting upstream of Wnt4 in nephrogenesis.

    Evidence Co-culture of Wnt6-expressing cells with embryonic kidney mesenchyme; Wnt4-mutant rescue; Xenopus secondary axis assay

    PMID:11948913

    Open questions at the time
    • Receptor mediating Wnt6 signaling in kidney not identified
    • Endogenous requirement (loss-of-function in mammalian kidney) not tested
  3. 2005 High

    Identification of Wnt6 as an ectodermal signal promoting limb myogenesis via Pax3/Myf5 and simultaneously inhibiting chondrogenesis (via Sox9 repression) revealed WNT6 as a key ectodermal organizer of limb mesenchymal fate.

    Evidence Ectopic Wnt6 expression and ectoderm ablation in chick limb bud with in situ hybridization for myogenic and chondrogenic markers

    PMID:16271265 PMID:20334703

    Open questions at the time
    • Canonical vs. non-canonical pathway usage in limb myogenesis not resolved
    • Direct Wnt6 receptor in limb mesenchyme unknown
  4. 2007 High

    Two parallel discoveries showed WNT6 activates canonical β-catenin–Snail1 signaling for primitive endoderm epithelialization in F9 cells, yet uses a non-canonical pathway for neural crest induction in chick, establishing context-dependent pathway selection.

    Evidence Wnt6 conditioned medium and overexpression in F9 cells with β-catenin/Snail1 nuclear translocation; in ovo Wnt6 gain/loss-of-function with canonical vs. non-canonical reporters in chick

    PMID:17685490 PMID:18160257

    Open questions at the time
    • Molecular basis for pathway switching between canonical and non-canonical unknown
    • Non-canonical receptor and transducer in neural crest not identified
  5. 2008 High

    Wnt6 loss-of-function in Xenopus causing enlarged hearts, rescued by GATA, established WNT6 as a repressor of cardiomyogenesis via suppression of cardiogenic transcription factors.

    Evidence Xenopus morpholino knockdown; activated canonical Wnt gain-of-function; GATA rescue epistasis

    PMID:18804460

    Open questions at the time
    • Mammalian heart phenotype of Wnt6 loss not reported
    • Direct vs. indirect repression of GATA factors unresolved
  6. 2011 High

    β-catenin epistasis experiments confirmed that WNT6 inhibits adipogenesis and promotes osteoblastogenesis through an obligate β-catenin-dependent mechanism in mesenchymal progenitors.

    Evidence Gain/loss-of-function in ST2 and 3T3-L1 cells; β-catenin knockdown abolishes effects

    PMID:21872687

    Open questions at the time
    • Receptor identity for Wnt6 in mesenchymal stem cells not determined
    • In vivo bone/fat phenotype of Wnt6 knockout not examined
  7. 2012 High

    ChIP demonstrated that GATA6 and FOXA2 directly bind the WNT6 promoter, and separately that Caveolin-1/β-catenin binds the WNT6 promoter in gastric cancer, establishing the transcriptional regulation of WNT6 itself.

    Evidence ChIP and promoter reporter assays in F9 cells (GATA6/FOXA2) and gastric cancer cells (Cav1/β-catenin)

    PMID:22370641 PMID:22607194

    Open questions at the time
    • Whether WNT6 autoregulation via β-catenin creates a positive feedback loop in normal tissue not tested
    • Chromatin accessibility and epigenetic regulation of WNT6 locus unexplored
  8. 2013 High

    Three advances defined WNT6 functions in uterine decidualization (via cyclin B1), macrophage biology (ERK–c-Myc proliferation and M2 polarization), and Drosophila appendage development, broadening WNT6's known tissue repertoire.

    Evidence Wnt6-mutant mouse uterine stromal cells; Wnt6 conditioned medium on macrophages with pertussis toxin/ERK inhibition; Drosophila Wnt6 CRISPR knockout

    PMID:23175771 PMID:24090348 PMID:24123681

    Open questions at the time
    • Macrophage receptor for Wnt6 not identified
    • How Wnt6 activates pertussis toxin-sensitive Gαi in macrophages is mechanistically unclear
  9. 2015 High

    Sfrp2 was shown to bind Wnt6 and switch signaling from canonical to non-canonical JNK/PCP in cardiac progenitor cells, providing a molecular mechanism for the canonical/non-canonical pathway toggle.

    Evidence Sfrp2-Wnt6 binding assay; canonical Wnt reporter inhibition; JNK activation and CPC differentiation assays

    PMID:26071893

    Open questions at the time
    • Structural basis of Sfrp2-Wnt6 interaction not determined
    • Whether other SFRPs similarly toggle Wnt6 signaling unknown
  10. 2016 High

    FZD7 was identified as a WNT6 receptor in renal epithelial cells, with Wnt6 signaling through GSK3β phosphorylation/β-catenin nuclear accumulation and additionally blocking TGF-β–NF-κB crosstalk.

    Evidence TCF/LEF reporter; GSK3β phosphorylation; β-catenin fractionation; p65 localization; p65−/− and IKKα/β−/− fibroblasts

    PMID:27122540

    Open questions at the time
    • Whether FZD7 is the primary receptor in other WNT6-responsive tissues not established
    • Co-receptor (LRP5/6) requirement not formally tested
  11. 2019 High

    FZD4 was identified as a second WNT6 receptor, mediating canonical signaling upstream of ROCK1 and 14-3-3σ to drive centrosome amplification under diabetic conditions.

    Evidence siRNA and neutralizing antibodies against Wnt6/FZD4; β-catenin nuclear translocation; centrosome counting in diabetic mouse colon

    PMID:31618077

    Open questions at the time
    • Whether FZD4 and FZD7 serve redundant or tissue-specific roles for WNT6 is unknown
    • Direct Wnt6–FZD4 physical binding not shown by biophysical methods
  12. 2021 High

    WNT6 was shown to promote macrophage foam cell formation via ACC2-dependent triacylglycerol storage, directly linking WNT6 to lipid metabolism and Mycobacterium tuberculosis intracellular survival.

    Evidence Wnt6-deficient macrophages; ACC2 pharmacological inhibition; intracellular TAG quantification; Mtb survival in vitro and in vivo

    PMID:34255743

    Open questions at the time
    • How WNT6 regulates ACC2 expression or activity at the molecular level not defined
    • Whether this pathway operates in human TB macrophages in patients not confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of WNT6–Frizzled selectivity, the molecular switch determining canonical versus non-canonical pathway engagement, the phenotype of mammalian Wnt6 complete knockout across tissues, and whether WNT6 lipid modifications govern receptor specificity.
  • No crystal structure or cryo-EM of WNT6–receptor complex
  • No comprehensive mammalian Wnt6 knockout phenotyping across organ systems
  • Mechanism of canonical/non-canonical switch at the receptor level unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 7 GO:0098772 molecular function regulator activity 5
Localization
GO:0005576 extracellular region 6
Pathway
R-HSA-162582 Signal Transduction 9 R-HSA-1266738 Developmental Biology 7 R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 2
Partners
ACC2CTNNB1FZD4FZD7SFRP2SULF1

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 Wnt6, Wnt10a, and Wnt10b inhibit adipogenesis and stimulate osteoblastogenesis through a β-catenin-dependent mechanism; knockdown of β-catenin completely prevents these effects, establishing that downstream mechanisms of β-catenin are required for Wnt6 to influence mesenchymal stem cell fate. Gain- and loss-of-function in ST2 and 3T3-L1 cells; β-catenin knockdown epistasis; β-catenin stabilization assays Bone High 21872687
2001 Human WNT6 encodes a 365-amino-acid secreted glycoprotein with an N-terminal signal peptide, WNT core domain, and RGD motif; the WNT6 and WNT10A genes are clustered head-to-tail within 7 kb on chromosome 2q35. Molecular cloning, sequence analysis, Northern blot expression analysis Biochemical and biophysical research communications Medium 11350055
2002 Wnt-6 expressed in the ureter bud induces kidney tubulogenesis in vitro, rescues tubulogenesis in Wnt-4 mutant embryonic mesenchyme, and activates Wnt-4 transcription, placing Wnt-6 upstream of Wnt-4 in the tubulogenesis pathway; Wnt-6 also induces a secondary axis in Xenopus embryos, consistent with canonical pathway activation. Cell lines expressing Wnt-6 co-cultured with embryonic kidney mesenchyme; Wnt-4 mutant rescue assay; Xenopus secondary axis assay; in situ hybridization for tubulogenesis markers Genesis High 11948913
2007 Wnt6 induces specification and epithelialization of F9 embryonal carcinoma cells to primitive endoderm via a canonical Wnt6–β-catenin–Snail1 signaling cascade, involving nuclear translocation of β-catenin and Snail1 and appearance of cytokeratin intermediate filaments. Wnt6 conditioned medium treatment; Wnt6-expressing cell lines; LiCl GSK-3 inhibition; immunofluorescence for β-catenin and Snail1 nuclear translocation; cytokeratin staining; PKA activation for parietal endoderm EMT Cellular signalling High 18160257
2007 In chick embryos, Wnt6 derived from the surface ectoderm is necessary for neural crest induction and acts through the non-canonical (not β-catenin-dependent) signaling pathway; canonical Wnt signaling inhibited neural crest production in chick. In ovo Wnt6 loss-of-function and gain-of-function; canonical vs. non-canonical pathway reporter assays in chick embryos Developmental dynamics High 17685490
2008 Wnt6 in Xenopus is required during organogenesis to restrict heart muscle development; Wnt6 loss-of-function results in abnormally large heart muscle, and this repressive role is mediated via repression of cardiogenic transcription factors (including GATA), since reinstating GATA function rescues cardiomyogenic differentiation. Xenopus loss-of-function (morpholinos); gain-of-function with activated canonical Wnt/β-catenin; GATA rescue epistasis; analysis of cardiogenic transcription factors and differentiation genes Developmental biology High 18804460
2005 Ectodermal Wnt-6 promotes limb myogenesis through a Pax3/Paraxis–Myf5 pathway in chick; ectopic Wnt-6 expression extends domains of Pax3, Paraxis, Myf5, Myogenin, Desmin, and MyHC while inhibiting MyoD, and rescues myogenic gene expression after ectoderm removal, identifying a distinct Wnt-6 pathway separate from a MyoD-dependent ectodermal signal. Ectopic Wnt-6 expression in chick limb bud in ovo; ectoderm removal; in situ hybridization for myogenic markers Developmental biology High 16271265
2006 Neural tube-derived Wnt1 and Wnt3a inhibit Wnt6 expression in the medial surface ectoderm via dermomyotomal Wnt11; Wnt11 was identified as an epithelialization factor acting on the medial dermomyotome, placing Wnt6 and Wnt11 as factors maintaining the epithelial nature of the ventrolateral and dorsomedial dermomyotomal lips, respectively. Interference with neighboring signaling pathways in chick embryo; in ovo gain/loss-of-function; in situ hybridization Development Medium 16818447
2010 Ectodermal Wnt6 acts as a negative regulator of limb chondrogenesis in the chick embryo; ectoderm ablation leads to ectopic Sox9 and Collagen II expression, and Wnt6 overexpression reduces Sox9 and Collagen II, placing Wnt6 upstream of Sox9 in the chondrogenic cascade. Ectoderm ablation in chick limb bud; ectopic Wnt6 expression; in situ hybridization for Sox9, Collagen II BMC developmental biology High 20334703
2013 Wnt6 is essential for uterine stromal cell proliferation during decidualization in mice; Wnt6 deficiency impairs stromal cell proliferation by downregulating cyclin B1 expression and prolonging cell cycle length, without adversely affecting decidual polyploidization. Wnt6-mutant mouse analysis; primary stromal cell culture; cell cycle analysis; cyclin B1 expression assay Biology of reproduction High 23175771
2013 Wnt6 induces macrophage proliferation via a pertussis toxin-sensitive, ERK-mediated, β-catenin-independent induction of c-Myc; Wnt6 also drives macrophage polarization toward an M2-like phenotype by inducing Arginase-1 and downregulating TNF-α; Wnt6 expression in macrophages is induced via a TLR–MyD88–NF-κB-dependent pathway. Wnt6 conditioned medium treatment of macrophages; Wnt6-deficient macrophage analysis; thymidine incorporation proliferation assay; Ki-67 expression; pertussis toxin inhibition; ERK pathway analysis; Arginase-1 and TNF-α measurement Journal of immunology High 24123681
2021 WNT6 promotes foam cell formation in macrophages by regulating acetyl-CoA carboxylase 2 (ACC2) and triacylglycerol (TAG) storage; genetic or pharmacological loss of WNT6 or ACC2 significantly reduced intracellular TAG levels and Mycobacterium tuberculosis survival in macrophages. Genetic (Wnt6-deficient macrophages) and pharmacological (ACC2 inhibitor) approaches; intracellular TAG measurement; Mtb survival assay; in vivo mouse TB model Journal of Clinical Investigation High 34255743
2015 Sfrp2 binds Wnt6 and inhibits Wnt6 canonical signaling in cardiac progenitor cells (CPCs), which is required for inhibition of CPC proliferation; this canonical Wnt6 inhibition by Sfrp2 activates the non-canonical Wnt/PCP pathway through JNK, inducing cardiac transcription factors and CPC differentiation. Sfrp2-Wnt6 binding assay; canonical Wnt pathway reporter; JNK activation assay; CPC proliferation and differentiation assays; loss-of-function experiments Journal of molecular and cellular cardiology High 26071893
2016 Wnt6 signals through the canonical pathway in renal epithelial cells via the FZD7 receptor, as evidenced by increased GSK3β phosphorylation (Ser9), nuclear accumulation of β-catenin, and increased TCF/Lef transcriptional activity; Wnt6 also inhibits TGF-β-mediated p65-NF-κB nuclear translocation and rescues epithelial dedifferentiation. TCF/Lef reporter assay; GSK3β phosphorylation Western blot; β-catenin nuclear fractionation; 3D tubulogenesis assay; TGF-β rescue experiments; p65-NF-κB localization; p65(-/-) and IKKα/β(-/-) fibroblast experiments American journal of physiology. Renal physiology High 27122540
2009 Wnt6 overexpression in human dental papilla cells enhances odontoblast-like differentiation (increased ALPase activity, upregulation of ALP, Col I, ON, OPN, BSP, DMP-1 gene expression, and mineral deposition) without significant effect on cell proliferation. Recombinant adenovirus Wnt6 overexpression; BrdU incorporation assay; flow cytometry; ALPase activity assay; mineralization assay; gene expression analysis Journal of endodontics Medium 20113781
2014 WNT6 activates the JNK (c-Jun N-terminal kinase) non-canonical signaling pathway in human dental pulp cells, promoting cell migration and odontoblast-like differentiation; blockage of JNK with SP600125 decreases but does not completely abolish WNT6-induced migration and differentiation, indicating additional pathway involvement. WNT6 conditioned medium treatment; JNK inhibitor SP600125; Western blot for JNK activation; RT-PCR for c-Jun; wound healing and transwell migration assays; ALP and Alizarin red staining; odontogenic gene expression Journal of endodontics Medium 24935540
2012 GATA6 and FOXA2 transcription factors directly bind the Wnt6 promoter and are sufficient to activate Wnt6 gene expression, leading to canonical WNT-β-catenin pathway activation and primitive endoderm induction in F9 cells. Chromatin immunoprecipitation (ChIP); Wnt6 promoter reporter assay; GATA6/FOXA2 overexpression; TCF-dependent transcription assay Stem cells and development High 22607194
2009 Coordinate Gα13–RhoA and Wnt6–β-catenin signaling are both required for retinoic acid-induced differentiation of F9 cells to primitive endoderm; Gα13/p115RhoGEF (but not RhoA alone) causes β-catenin nuclear translocation, and two independent pathways (canonical Wnt-β-catenin and Gα13-ERM) must both be active for primitive endoderm formation. Constitutively active Gα13(Q226L), p115RhoGEF, and RhoA(L63) overexpression; dominant-negative constructs; ROCK inhibitor Y-27632; β-catenin nuclear localization assay; F9 differentiation markers Biochemistry and cell biology Medium 19767821
2012 Caveolin-1 (Cav1) promotes WNT6 expression in gastric cancer cells; epirubicin increases WNT6 promoter activity through Cav1-dependent binding of β-catenin to the proximal WNT6 promoter; WNT6 increases resistance to epirubicin/doxorubicin-induced apoptosis. WNT6 knockdown and overexpression; WNT6 promoter reporter assay; β-catenin ChIP on WNT6 promoter; apoptosis assays; Cav1 manipulation Oncogene High 22370641
2018 PLAGL2 transcriptionally activates WNT6 by directly binding to its promoter region, thereby activating the Wnt/β-catenin pathway and promoting colorectal cancer cell proliferation. ChIP assay; dual-luciferase reporter assay; PLAGL2 knockdown; Wnt/β-catenin pathway gene expression analysis; xenograft model Oncology reports High 30535429
2019 Secreted Wnt6 binds to receptor FZD4 to activate canonical β-catenin signaling, which is upstream of ROCK1 and 14-3-3σ, mediating diabetes-associated centrosome amplification; antibodies against Wnt6 or FZD4, or siRNA knockdown of either, attenuate centrosome amplification induced by high glucose/insulin/palmitic acid or advanced glycation end products (AGEs). siRNA knockdown of Wnt6, FZD4, β-catenin; neutralizing antibodies against Wnt6 and FZD4; β-catenin nuclear translocation assay; centrosome amplification quantification; in vivo diabetic mouse colon tissue analysis American journal of physiology. Cell physiology High 31618077
2020 Wnt6 overexpression in the amygdala of MeCP2 T158A mice ameliorates behavioral deficits; Wnt6 restores GSK-3β phosphorylation and reduces β-catenin phosphorylation, restores MeCP2 SUMOylation, and increases BDNF and IGF-1 expression through activation of their promoters in a dose-dependent manner. Lentiviral Wnt6 delivery to amygdala; behavioral testing; Western blot for GSK-3β/β-catenin phosphorylation; SUMOylation assay; Bdnf/Igf-1 promoter reporter in HEK293T cells; RT-PCR and protein expression Scientific reports Medium 31974426
2019 HBCD (hexabromocyclododecane) promotes adipogenesis by specifically inhibiting Wnt6 gene expression and thereby suppressing the Wnt/β-catenin pathway at an early stage of adipogenesis; this was demonstrated both in cultured preadipocytes and in vivo in mice. RNA sequencing; Wnt6 expression analysis; adipogenesis assays in 3T3-L1 and HPA-V cells; in vivo epididymal fat analysis in C57BL/6 mice; Wnt/β-catenin pathway markers The Science of the total environment Medium 31865202
2018 In Drosophila ovaries, Wnt6 produced by cap cells is required to maintain anterior escort cells as a niche component; loss of Wnt6 signaling causes anterior escort cell death, leading to loss of germline stem cells; anterior escort cells maintain GSCs by promoting DE-cadherin anchorage and transient Dpp/BMP signaling. Drosophila genetic loss-of-function; hid expression-induced escort cell death; GSC counting; immunostaining for DE-cadherin, Dpp; live imaging Development High 29361569
2021 In Drosophila testis, Wnt6 regulates germline stem cell differentiation and cyst stem cell self-renewal via non-canonical Wnt signaling through Rac1 and Cdc42; Wnt6 downregulates Arm (β-catenin), Rac1, and Cdc42 in S2 cells, and Rac1/Cdc42 act downstream of Wnt6 in the niche. Drosophila genetic manipulation; Schneider 2 (S2) cell Wnt6 manipulation; Rac1, Cdc42, Arm protein level measurement; rescue epistasis experiments Experimental cell research Medium 33582096
2013 Wnt6 is required for maxillary palp development in Drosophila; Wnt6 knockout flies lack maxillary palps but show no defects in wing size or planar cell polarity. CRISPR/homologous recombination Wnt6 knockout in Drosophila; morphological analysis of maxillary palps and wings BMC biology High 24090348
2011 Maternal Wnt6 is necessary for endoderm specification in sea urchin embryos via canonical Wnt/β-catenin pathway activation; Wnt6 knockdown produces embryos lacking endoderm but retaining mesoderm markers; Wnt6 acts together with a localized vegetal cortical Dishevelled (Dsh) concentration to activate the endomesoderm gene regulatory network. Morpholino knockdown in sea urchin; vegetal cortex ablation and rescue with Wnt6; activated β-catenin/DN-GSK-3β/Dsh rescue; in situ hybridization for endoderm and mesoderm markers Development Medium 21750039
2012 Sulf1A is required for Wnt6-induced cellular hyper-elongation and inhibition of proliferation in myoblasts; Sulf1A neutralizing antibodies abolish both Wnt6-induced effects, demonstrating Sulf1A as a regulator of Wnt6 signaling in skeletal muscle. Wnt6 conditioned medium treatment of satellite cells on single fibres; Sulf1A neutralizing antibody treatment; proliferation and morphology assays FEBS open bio Medium 23772371
2022 Wnt6 activates the β-catenin-dependent canonical pathway in human dental papilla cells, as shown by β-catenin nuclear accumulation, LEF1 upregulation, and enhanced TCF/Lef transcriptional activity; Wnt6 inhibits odontogenic differentiation in vitro but promotes mineralization after subcutaneous transplantation in vivo; XAV939 (Wnt/β-catenin inhibitor) attenuates Wnt6-induced mineralization. Wnt6 overexpression and knockdown; immunofluorescence for nuclear β-catenin; qPCR for LEF1; TOPflash/FOPflash dual-luciferase reporter; ALP staining; Alizarin Red; subcutaneous transplantation; XAV939 inhibitor treatment Archives of oral biology Medium 35691114
2017 Wnt6 promotes viability and cell cycle progression (increasing S and G2/M phases) of mouse embryonic palatal mesenchymal cells through activation of the β-catenin signaling pathway; blockade of Wnt/β-catenin reduces Wnt6-induced cell viability. Recombinant Wnt6 treatment; MTT assay; flow cytometric cell cycle analysis; dual luciferase assay for β-catenin pathway; β-catenin pathway blockade Experimental and therapeutic medicine Medium 29285061
2021 In mouse embryonic stem cells, WNT6 silencing partially impairs endothelial differentiation induced by BMP4, and this dysfunction is rescued by addition of recombinant WNT6, placing WNT6 downstream of BMP4 in the endothelial commitment pathway. WNT6 siRNA silencing in ES/PA6 co-culture; recombinant WNT6 rescue; microarray gene expression profiling; endothelial differentiation assays Angiogenesis Medium 34478025
2022 Siglec6 overexpression in trophoblasts downregulates WNT6 secretion, impairing vascular endothelial cell functions (proliferation, migration, invasion, tube formation); recombinant human Wnt6 reverses Siglec6-conditioned medium-mediated HUVEC suppression by reactivating the Wnt/β-catenin signaling pathway. Siglec6 overexpression; transcriptome sequencing; qPCR and ELISA for Wnt6; HUVEC functional assays; recombinant Wnt6 rescue; Wnt/β-catenin pathway analysis Archives of biochemistry and biophysics Medium 36113626
2020 Eif2s3y promotes spermatogonial stem cell (SSC) proliferation via activation of the Wnt6/β-catenin signaling pathway; transgenic Eif2s3y mice have increased active β-catenin and elevated Wnt6 expression, identifying Eif2s3y–Wnt6–β-catenin as a regulatory axis in spermatogenesis. Transgenic Eif2s3y mouse generation; SSC proliferation assay; active β-catenin and Wnt6 protein/mRNA expression analysis by Western blot and qPCR Biochimica et biophysica acta. Molecular cell research Medium 32621839

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Wnt6, Wnt10a and Wnt10b inhibit adipogenesis and stimulate osteoblastogenesis through a β-catenin-dependent mechanism. Bone 355 21872687
2001 WNT10A and WNT6, clustered in human chromosome 2q35 region with head-to-tail manner, are strongly coexpressed in SW480 cells. Biochemical and biophysical research communications 153 11350055
2002 Wnt6 marks sites of epithelial transformations in the chick embryo. Mechanisms of development 80 12175501
2012 WNT6 is a novel target gene of caveolin-1 promoting chemoresistance to epirubicin in human gastric cancer cells. Oncogene 77 22370641
2002 Wnt-6 is expressed in the ureter bud and induces kidney tubule development in vitro. Genesis (New York, N.Y. : 2000) 73 11948913
2013 Wnt6 is expressed in granulomatous lesions of Mycobacterium tuberculosis-infected mice and is involved in macrophage differentiation and proliferation. Journal of immunology (Baltimore, Md. : 1950) 66 24123681
2013 Wnt6 is essential for stromal cell proliferation during decidualization in mice. Biology of reproduction 60 23175771
2011 Wnt6 activates endoderm in the sea urchin gene regulatory network. Development (Cambridge, England) 52 21750039
2018 Wnt6 maintains anterior escort cells as an integral component of the germline stem cell niche. Development (Cambridge, England) 46 29361569
2005 Ectodermal Wnt-6 promotes Myf5-dependent avian limb myogenesis. Developmental biology 46 16271265
2018 Overexpressed PLAGL2 transcriptionally activates Wnt6 and promotes cancer development in colorectal cancer. Oncology reports 44 30535429
2007 Wnt6 induces the specification and epithelialization of F9 embryonal carcinoma cells to primitive endoderm. Cellular signalling 41 18160257
2007 Wnt6 controls amniote neural crest induction through the non-canonical signaling pathway. Developmental dynamics : an official publication of the American Association of Anatomists 37 17685490
2008 Wnt6 signaling regulates heart muscle development during organogenesis. Developmental biology 36 18804460
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
2005 Identification and characterization of rat Wnt6 and Wnt10a genes in silico. International journal of molecular medicine 34 15702249
2009 Effect of Wnt6 on human dental papilla cells in vitro. Journal of endodontics 33 20113781
2015 Inhibition of Wnt6 by Sfrp2 regulates adult cardiac progenitor cell differentiation by differential modulation of Wnt pathways. Journal of molecular and cellular cardiology 32 26071893
2021 WNT6/ACC2-induced storage of triacylglycerols in macrophages is exploited by Mycobacterium tuberculosis. The Journal of clinical investigation 29 34255743
2016 Wnt6 regulates epithelial cell differentiation and is dysregulated in renal fibrosis. American journal of physiology. Renal physiology 27 27122540
2003 Spatial and temporal pattern of Wnt-6 expression during chick development. Anatomy and embryology 27 12695910
2012 GATA6 and FOXA2 regulate Wnt6 expression during extraembryonic endoderm formation. Stem cells and development 26 22607194
2020 Expression and Function of WNT6: From Development to Disease. Frontiers in cell and developmental biology 23 33425886
2011 Polymorphisms in WNT6 and WNT10A and colorectal adenoma risk. Nutrition and cancer 23 21547848
2008 Wnt6 expression in epidermis and epithelial tissues during Xenopus organogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 22 18224714
2016 Molecular cloning, characterization and expression analysis of Wnt4, Wnt5, Wnt6, Wnt7, Wnt10 and Wnt16 from Litopenaeus vannamei. Fish & shellfish immunology 21 27153750
2013 Wnt6 is required for maxillary palp formation in Drosophila. BMC biology 21 24090348
2013 Cloning and expression analysis of Wnt6 and Hox6 during intestinal regeneration in the sea cucumber Apostichopus japonicus. Genetics and molecular research : GMR 21 24301793
2020 Restoring Wnt6 signaling ameliorates behavioral deficits in MeCP2 T158A mouse model of Rett syndrome. Scientific reports 20 31974426
2019 Exposure to HBCD promotes adipogenesis both in vitro and in vivo by interfering with Wnt6 expression. The Science of the total environment 19 31865202
2018 Wnt6 contributes tumorigenesis and development of colon cancer via its effects on cell proliferation, apoptosis, cell-cycle and migration. Oncology letters 19 29963191
2010 Ectodermal Wnt6 is an early negative regulator of limb chondrogenesis in the chicken embryo. BMC developmental biology 18 20334703
2014 WNT6 promotes the migration and differentiation of human dental pulp cells partly through c-Jun N-terminal kinase signaling pathway. Journal of endodontics 17 24935540
2012 Follicle characteristics and follicle developmental related Wnt6 polymorphism in Chinese indigenous Wanxi-white goose. Molecular biology reports 17 22714925
2021 Wnt6 plays a complex role in maintaining human limbal stem/progenitor cells. Scientific reports 16 34686698
2020 Eif2s3y regulates the proliferation of spermatogonial stem cells via Wnt6/<beta>-catenin signaling pathway. Biochimica et biophysica acta. Molecular cell research 14 32621839
2020 Long non-coding RNA366.2 controls endometrial epithelial cell proliferation and migration by upregulating WNT6 as a ceRNA of miR-1576 in sheep uterus. Biochimica et biophysica acta. Gene regulatory mechanisms 14 32679187
2017 Wnt6 influences the viability of mouse embryonic palatal mesenchymal cells via the β-catenin pathway. Experimental and therapeutic medicine 14 29285061
2015 Increased WNT6 expression in tumor cells predicts unfavorable survival in esophageal squamous cell carcinoma patients. International journal of clinical and experimental pathology 14 26617869
2012 Role of Sulf1A in Wnt1- and Wnt6-induced growth regulation and myoblast hyper-elongation. FEBS open bio 13 23772371
2022 LncRNA PVT1 Regulates miR-1207-5p to Affect Colon Cancer Proliferation and Migration via the Wnt6/β-catenin2 Pathway. Genetic testing and molecular biomarkers 12 35763386
2009 Coordinate Galpha13 and Wnt6-beta-catenin signaling in F9 embryonal carcinoma cells is required for primitive endoderm differentiation. Biochemistry and cell biology = Biochimie et biologie cellulaire 11 19767821
2019 Secreted Wnt6 mediates diabetes-associated centrosome amplification via its receptor FZD4. American journal of physiology. Cell physiology 10 31618077
2018 Non-canonical WNT6/WNT10A signal factor expression in EBV+ post-transplant smooth muscle tumors. Clinical sarcoma research 10 29881541
2022 Wnt4, Wnt6 and β-catenin expression in human placental tissue - is there a link with first trimester miscarriage? Results from a pilot study. Reproductive biology and endocrinology : RB&E 9 35300692
2023 The investigation of WNT6 and WNT10A single nucleotide polymorphisms as potential biomarkers for dental pulp calcification in orthodontic patients. PloS one 8 37566620
2022 Elevated trophoblastic Siglec6 contributes to the impairment of vascular endothelial cell functions by downregulating Wnt6/β-catenin signaling in preeclampsia. Archives of biochemistry and biophysics 8 36113626
2015 Novel missense mutation in WNT6 in 100 couples with unexplained recurrent miscarriage. Human reproduction (Oxford, England) 8 25750203
2021 Roles of WNT6 in Sheep Endometrial Epithelial Cell Cycle Progression and Uterine Glands Organogenesis. Veterinary sciences 7 34941843
2019 High WNT6 expression indicates unfavorable survival outcome for patients with colorectal liver metastasis after liver resection. Journal of Cancer 7 31258769
2017 Correlation study of DNA methylation of WNT6 gene with osteosarcoma in children. Oncology letters 7 28693164
2023 Identification of Functional Modules and Key Pathways Associated with Innervation in Graft Bone-CGRP Regulates the Differentiation of Bone Marrow Mesenchymal Stem Cells via p38 MAPK and Wnt6/β-Catenin. Stem cells international 6 37621747
2022 WNT6 participates in the occurrence and development of ovarian cancer by upregulating/activating the typical Wnt pathway and Notch1 signaling pathway. Gene 6 36075327
2021 Wnt6 regulates the homeostasis of the stem cell niche via Rac1-and Cdc42-mediated noncanonical Wnt signalling pathways in Drosophila testis. Experimental cell research 6 33582096
2021 Role of TGFβ1 and WNT6 in FGF2 and BMP4-driven endothelial differentiation of murine embryonic stem cells. Angiogenesis 6 34478025
2020 MiR-566 protects the malignant progression of breast cancer by negatively regulating WNT6. European review for medical and pharmacological sciences 6 32572884
2025 Clofazimine enhances anti-PD-1 immunotherapy in glioblastoma by inhibiting Wnt6 signaling and modulating the tumor immune microenvironment. Cancer immunology, immunotherapy : CII 3 40053076
2022 The glycoprotein Wnt6 regulates human dental papilla cells differentiation by canonical Wnt signaling pathway. Archives of oral biology 3 35691114
2024 Emerging roles and biomarker potential of WNT6 in human cancers. Cell communication and signaling : CCS 2 39529066
2015 [EFFECT OF WNT6 IN PROLIFERATION, DIFFERENTIATION, AND MIGRATION OF BONE MARROW MESENCHYMAL STEM CELLS]. Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery 2 26455179
2025 Wnt6 and Wnt10 regulate spot marking formation in Bombyx mori larvae. Insect science 1 40717501
2024 The expression pattern of Wnt6, Wnt10A, and HOXA13 during regenerating tails of Gekko Japonicus. Gene expression patterns : GEP 1 39128795
2026 Ectopic Wnt6 expression induces twin-spot markings in the epidermis of the silkworm Bombyx mori - Potential molecular target to discover evolutionary mechanisms of adaptive body coloration in insects. The FEBS journal 0 41928441
2025 WNT6 promotes choriocarcinoma progression by driving proliferation, invasion, and metastasis. Discover oncology 0 41258626