Affinage

FZD5

Frizzled-5 · UniProt Q13467

Length
585 aa
Mass
64.5 kDa
Annotated
2026-06-09
47 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FZD5 is a class F seven-transmembrane GPCR that serves as a ligand-specific WNT receptor controlling endothelial growth, trophoblast morphogenesis, neural patterning, and stem cell self-renewal (PMID:11092808, PMID:23610556, PMID:38358799). It binds WNT ligands directly through its extracellular cysteine-rich domain, including a nanomolar-affinity interaction with WNT7A and surface-plasmon-resonance-measured binding of WNT5A (PMID:18230341, PMID:29930766), and assembles ligand-specific complexes with the co-receptor LRP6/LRP5 to stabilize beta-catenin and drive TCF/LEF transcription (PMID:12857724, PMID:35295855, PMID:38358799). Upon WNT-5A stimulation FZD5 undergoes a GPCR-like conformational change and couples to Galphaq, activating intracellular Ca2+ release and PKC/CaMKII signaling as well as NFkB-driven transcription (PMID:30514810, PMID:25240054, PMID:37951508). Through these branches FZD5 sustains endothelial proliferation and angiogenesis (PMID:11092808, PMID:25240054, PMID:29845518), drives chorionic branching via a Gcm1 positive-feedback loop coupled to junctional remodeling (PMID:23610556), and is the selective WNT receptor required for proliferation of RNF43-mutant pancreatic tumors (PMID:27869803). FZD5 abundance is set by ZNRF3/RNF43-dependent endocytosis and lysosomal degradation upon WNT stimulation (antagonized by RSPO1) and by CVAK104-mediated basal lysosomal turnover (PMID:41070826, PMID:19643732), and its expression is further controlled transcriptionally by DNMT3A promoter methylation and post-transcriptionally by m6A/YTHDF1 translation and lncRNA HIDEN/IMP1 mRNA stabilization (PMID:38707304, PMID:33230473, PMID:37095549). A heterozygous frameshift mutation producing a secreted, dominant-negative truncated FZD5 causes coloboma and microphthalmia (PMID:26908622).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2001 High

    Established FZD5 as a developmentally essential WNT receptor by showing its loss is embryonic-lethal due to a specific angiogenic-proliferation defect, the first in vivo proof it transduces WNT signals.

    Evidence Knockout mouse with BrdU proliferation assay plus Xenopus ectopic-axis synergy with WNT2/5A/10B

    PMID:11092808

    Open questions at the time
    • Did not define the downstream signaling branch responsible for the proliferation defect
    • Ligand-receptor binding not demonstrated biochemically
  2. 2003 Medium

    Defined the receptor architecture by showing FZD5 partners with LRP6 to transduce a specific WNT ligand into canonical beta-catenin/TCF signaling.

    Evidence TCF/LEF reporter, beta-catenin stability assay and Dickkopf antagonism in PC12 cells

    PMID:12857724

    Open questions at the time
    • Single cell type
    • Direct WNT7A-FZD5 physical binding not shown here
  3. 2008 Medium

    Provided direct biochemical proof of ligand engagement, showing WNT7A binds the FZD5 cysteine-rich domain at nanomolar affinity.

    Evidence ELISA-based purified-protein binding assay and split-eGFP complementation in cells

    PMID:18230341

    Open questions at the time
    • Single lab/paper
    • No structural model of the complex
  4. 2009 High

    Revealed that FZD5 surface levels are actively controlled by trafficking, identifying CVAK104 as a selective regulator routing FZD5 to lysosomal degradation and thereby tuning WNT signaling output.

    Evidence Co-IP with FZD1/FZD4 selectivity controls, dominant-negative Rab5, RNAi, lysosomal inhibitors and beta-catenin reporter

    PMID:19643732

    Open questions at the time
    • Relationship to ligand-induced degradation pathway not addressed
    • Mechanism of CVAK104 substrate selectivity unclear
  5. 2013 High

    Placed FZD5 in a developmental morphogenetic circuit, showing it forms a Gcm1 positive-feedback loop and drives cell-junction disassembly to initiate chorionic branching.

    Evidence Global and trophoblast-specific KO mice, trophoblast stem cell lines, tetraploid aggregation, immunofluorescence and Western blot

    PMID:23610556

    Open questions at the time
    • How beta-catenin signaling selectively downregulates junctional proteins not resolved
  6. 2014 Medium

    Connected FZD5 to non-canonical Ca2+/NFkB signaling in angiogenesis, showing monocyte-derived WNT5A drives tissue-factor expression in endothelium.

    Evidence Paracrine co-culture, Ca2+ release, NFkB reporter, tube formation and in vivo microvessel assays

    PMID:25240054

    Open questions at the time
    • G-protein coupling not directly demonstrated
    • Single lab
  7. 2016 High

    Demonstrated a Mendelian disease mechanism: a secreted, transmembrane-less FZD5 fragment acts as a dominant-negative WNT decoy causing ocular coloboma/microphthalmia.

    Evidence Cell secretion assay, canonical/non-canonical reporters, zebrafish overexpression, mouse Fz5/Fz8 compound KO

    PMID:26908622

    Open questions at the time
    • Penetrance and human population frequency not addressed in mechanism studies
  8. 2016 High

    Identified FZD5 as a uniquely targetable WNT receptor in RNF43-mutant cancer, showing functional specificity not explained by expression level among the ten FZD receptors.

    Evidence Genome-wide CRISPR-Cas9 dropout screens, anti-FZD5 antibody panel, xenografts and patient-derived organoids

    PMID:27869803

    Open questions at the time
    • Structural basis of FZD5 functional uniqueness undefined
    • Ligand identity in this context not specified
  9. 2018 High

    Defined the proximal signaling mechanism, showing FZD5 behaves as a Galphaq-coupled GPCR undergoing WNT-5A-induced conformational change.

    Evidence Dual-color FRAP and RET-based assays with live-cell conformational imaging

    PMID:30514810

    Open questions at the time
    • Structure of the active conformation not solved
    • Which downstream branch each G protein selects not fully mapped
  10. 2018 Medium

    Dissected the angiogenic effector branch, showing FZD5 signals through PKC and Ets1 to control endothelial cycle and pro-angiogenic gene expression independently of canonical Wnt, Ca2+/NFAT, and PCP/JNK.

    Evidence siRNA knockdown, cell cycle and migration assays, 3D collagen tube formation, inhibitor-panel pathway dissection

    PMID:29845518

    Open questions at the time
    • Ligand driving this branch not identified
    • Single lab
  11. 2018 Medium

    Quantified WNT5A receptor preference, showing FZD5 binds WNT5A more strongly than RYK and is required for WNT5A's anti-proliferative effect in prostate cancer.

    Evidence Surface plasmon resonance and FZD5/RYK/FZD8 siRNA with proliferation/apoptosis readouts

    PMID:29930766

    Open questions at the time
    • Division of labor between FZD5 and RYK in cells not fully resolved
    • Single lab
  12. 2020 Medium

    Showed post-transcriptional control of FZD5, with m6A-dependent YTHDF1 boosting FZD5 translation to drive WNT/beta-catenin oncogenesis.

    Evidence Ribosome profiling/multi-omics, m6A analysis, YTHDF1 perturbation, in vitro and in vivo assays in HCC

    PMID:33230473

    Open questions at the time
    • Site-level m6A marks on FZD5 mRNA not mapped
    • Single lab
  13. 2020 Medium

    Linked FZD5 to a proliferative/DNA-repair program, identifying FOXM1 as a downstream effector and WNT7B as the relevant ligand in TNBC.

    Evidence FZD5 loss/gain-of-function with FOXM1 rescue, cell cycle and DNA damage repair assays

    PMID:33311446

    Open questions at the time
    • How FZD5 signaling activates FOXM1 mechanistically not defined
    • WNT7B-FZD5 binding not biochemically shown
  14. 2021 Medium

    Extended FZD5's role to stem cell maintenance, showing it restrains senescence in mesenchymal stem cells via non-canonical WNT and WNT5A.

    Evidence siRNA knockdown, overexpression, WNT5A treatment with senescence and proliferation assays

    PMID:33338299

    Open questions at the time
    • Specific non-canonical effectors not delineated
    • Single lab
  15. 2021 Medium

    Defined an EMT-suppressive function and its transcriptional regulation, mapping a PKC-ELF3-ZEB1 axis downstream and SNAI2/TEAD1 as upstream repressors of FZD5.

    Evidence ChIP-PCR, siRNA, PKC inhibitor, luciferase reporter and EMT marker analysis in gastric cancer

    PMID:33618713

    Open questions at the time
    • WNT7B/LRP5 partnership stated as putative
    • Context-dependence vs pro-tumor roles unresolved
  16. 2021 Medium

    Revealed receptor-tyrosine-kinase crosstalk, showing WNT5A/WNT11-FZD5 signaling cooperates with EGFR to drive cardiac fibrosis.

    Evidence TAC mouse model, bidirectional siRNA of WNT5A/WNT11/EGFR/FZD5, Masson staining and signaling Western blots

    PMID:34564708

    Open questions at the time
    • Molecular nature of FZD5-EGFR interaction not defined
    • Single lab
  17. 2022 Medium

    Confirmed a WNT5A-FZD5-LRP5 canonical self-renewal axis in endometrial stem-like cells using antibody neutralization.

    Evidence Anti-FZD5 neutralizing antibody, gene silencing, co-culture, TCF/LEF reporter and DKK1 inhibition

    PMID:35295855

    Open questions at the time
    • Reconciliation of WNT5A driving canonical signaling here vs non-canonical elsewhere not addressed
  18. 2023 Medium

    Established lncRNA-mediated mRNA stabilization as another control layer, with HIDEN-IMP1 stabilizing FZD5 mRNA to sustain WNT-dependent endoderm differentiation.

    Evidence shRNA/promoter deletion, RIP of IMP1-FZD5 mRNA, mRNA stability assay, WNT agonist rescue in human PSCs

    PMID:37095549

    Open questions at the time
    • IMP1 binding site on FZD5 mRNA not mapped
    • Single lab
  19. 2023 Medium

    Identified a secreted modulator, SFRP2, that binds FZD5 to promote Ca2+/CaMKII-Mek-Erk signaling and fibrosis in diabetic kidney disease.

    Evidence snRNA-seq, Co-IP of Sfrp2-Fzd5, Ca2+ measurement, perturbation and in vivo diabetic model

    PMID:37951508

    Open questions at the time
    • Whether SFRP2 acts as agonist vs ligand-presenting factor unclear
    • Single lab
  20. 2023 Medium

    Defined a hormonally regulated WNT7A-FZD5 axis maintaining fallopian tube stem cell self-renewal via canonical WNT signaling.

    Evidence Organoids, endogenous WNT reporter, single-cell and bulk transcriptomics, loss-of-function

    PMID:37917586

    Open questions at the time
    • Direct WNT7A-FZD5 binding in this system not shown
    • Single lab
  21. 2024 Medium

    Demonstrated FZD5's role in neural anterior-posterior patterning and its therapeutic targetability via selective FZD5/LRP6 clustering to generate dopaminergic neurons.

    Evidence Flow-cytometry receptor profiling and tetravalent FZD5/LRP6 bispecific antibody driving hPSC differentiation in vitro and in vivo

    PMID:38358799

    Open questions at the time
    • Endogenous WNT ligand for anterior FZD5 expression not identified
    • Single lab
  22. 2024 Medium

    Showed epigenetic transcriptional control, with DNMT3A binding the FZD5 promoter and silencing it via methylation, loss of which drives aberrant FZD5 in NSCLC.

    Evidence ChIP, methylation-specific PCR, DNMT3A overexpression in mouse, FZD5 siLNA in cells and in vivo

    PMID:38707304

    Open questions at the time
    • Specific methylated CpGs not mapped
    • Single lab
  23. 2025 High

    Resolved the ligand-induced degradation mechanism, showing WNT triggers ZNRF3/RNF43-dependent FZD5/8 endocytosis and degradation, antagonized by RSPO1 and distinct from DVL-driven basal endocytosis.

    Evidence Endocytosis/degradation assays, FZD5-RNF43 Co-IP, ZNRF3/RNF43 KO/KD, RSPO1 treatment, DVL loss-of-function

    PMID:41070826

    Open questions at the time
    • Ubiquitination sites on FZD5 not mapped
    • Relationship to CVAK104-mediated turnover not reconciled

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single receptor selects among canonical beta-catenin, Galphaq/Ca2+/PKC, and NFkB outputs in different tissues, and what determines its ligand- and context-specific functional uniqueness among FZD receptors.
  • No structure of an active FZD5-ligand-coreceptor complex
  • Rules governing branch selection across cell types unknown
  • Pro- versus anti-tumor context determinants undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 2 GO:0060089 molecular transducer activity 2 GO:0048018 receptor ligand activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005764 lysosome 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 2 R-HSA-5653656 Vesicle-mediated transport 2
Partners
CVAK104LRP5LRP6RNF43SFRP2WNT5AWNT7AWNT7B
Complex memberships
FZD5-LRP5 receptor complexFZD5-LRP6 receptor complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Fzd5 knockout mice die in utero around E10.75 due to defects in yolk sac and placental angiogenesis, with markedly reduced endothelial cell proliferation (BrdU labeling) prior to morphological changes; Fzd5 specifically synergized with Wnt2, Wnt5a, and Wnt10b in ectopic axis induction in Xenopus, establishing it as a Wnt receptor required for endothelial growth in the yolk sac. Homologous recombination knockout mouse, BrdU proliferation assay, Xenopus ectopic axis induction assay Development (Cambridge, England) High 11092808
2003 WNT7A signals specifically through a FZD5·LRP6 receptor complex in PC12 cells to increase β-catenin stability and activate TCF-based transcription; this activity is antagonized by Dickkopf-1 and Dickkopf-3. TCF/LEF luciferase reporter assay, β-catenin stability assay, dominant-negative receptor constructs, pharmacological inhibition with Dickkopf proteins in PC12 cells The Journal of biological chemistry Medium 12857724
2009 CVAK104 (a coated-vesicle-associated kinase) binds Dishevelled and selectively binds FZD5 (but not FZD1 or FZD4), induces clathrin-mediated intracellular accumulation of FZD5, and routes it to lysosomal degradation; CVAK104 knockdown increases FZD5 levels and activates Wnt/β-catenin signaling, while overexpression suppresses it. Co-immunoprecipitation, dominant-negative Rab5 assay, RNAi knockdown, lysosomal inhibitor experiments, Wnt/β-catenin reporter assay The Journal of biological chemistry High 19643732
2008 Purified Wnt7a directly binds the extracellular cysteine-rich domain of Fzd5 in the nanomolar range, as shown by ELISA-based protein-protein binding assay; a split eGFP complementation assay visualized Wnt7a-Fzd5 interactions and subsequent pathway activation in cells. ELISA-based protein binding assay with purified proteins, split eGFP complementation assay Biochemical and biophysical research communications Medium 18230341
2013 Fzd5 and Gcm1 form a positive feedback loop in chorionic trophoblast: Gcm1 upregulates Fzd5 specifically at branching initiation sites, and elevated Fzd5 expression maintains Gcm1 expression via nuclear β-catenin signaling. Fzd5-mediated signaling induces disassociation of cell junctions (downregulating ZO-1, claudin 4, claudin 7) for branching initiation and upregulates Vegf in chorion trophoblast cells. Global and trophoblast-specific Fzd5-null and Gcm1-deficient mouse models, trophoblast stem cell lines, tetraploid aggregation assay, immunofluorescence, Western blot PLoS biology High 23610556
2014 Monocyte-secreted Wnt5a activates FZD5 on microvascular endothelial cells, which signals through intracellular Ca2+ release and NFκB transcription to induce tissue factor (TF) expression, leading to angiogenesis by autocrine regulation. Paracrine co-culture assays, Ca2+ release measurement, NFκB reporter, in vitro tube formation and wound healing assay, in vivo microvessel formation assay Journal of molecular cell biology Medium 25240054
2016 A heterozygous frameshift mutation in FZD5 (p.Ala219Glufs*49) produces a truncated protein that retains the WNT-ligand-binding (cysteine-rich) domain but lacks the transmembrane domain; this truncated protein is secreted from cells and acts as a dominant-negative FZD5 receptor, antagonizing both canonical and non-canonical WNT signaling, causing coloboma and microphthalmia in zebrafish and disruption of retinal neural epithelium apical junctions in mouse. Cell secretion assay, dominant-negative functional assay (canonical and non-canonical WNT reporter), zebrafish overexpression, mouse conditional KO (Fz5/Fz8 compound) Human molecular genetics High 26908622
2016 Genome-wide CRISPR-Cas9 screens in RNF43-mutant PDAC cells identified FZD5 as the specific Wnt receptor required for proliferation in these tumors; anti-FZD5 antibodies inhibited growth in vitro and as xenografts in vivo, and the functional specificity of FZD5 could not be explained by differential protein expression patterns across the ten FZD receptors. Genome-wide CRISPR-Cas9 dropout screens, recombinant antibody panel, xenograft in vivo growth assay, patient-derived organoids Nature medicine High 27869803
2018 FZD5 is a Gαq-coupled seven-transmembrane receptor that undergoes conformational change upon WNT-5A stimulation (reminiscent of class A/B GPCR activation), activates Gαq and its downstream effectors, as demonstrated by dual-color FRAP and RET-based assays in live cells. Dual-color fluorescence recovery after photobleaching (dcFRAP), resonance energy transfer (RET)-based assays, live-cell imaging of conformational change Science signaling High 30514810
2018 In endothelial cells, FZD5 loss-of-function (siRNA) results in reduced proliferation (G0/G1 arrest), decreased migration, and enhanced expression of Angpt2 and Flt1 via enhanced PKC signaling and the transcription factor Ets1, without involvement of canonical Wnt, non-canonical Wnt/Ca2+-NFAT, or Wnt/PCP-JNK pathways. siRNA knockdown, cell cycle analysis, migration assays, 3D collagen co-culture tube formation, pathway inhibitor dissection, transcription factor (Ets1) mechanistic analysis Angiogenesis Medium 29845518
2018 Surface plasmon resonance analysis showed that WNT5A binds FZD5 with ~30% stronger binding response than to RYK; FZD5 knockdown completely abrogated the anti-proliferative effect of WNT5A in prostate cancer PC3 cells, while RYK knockdown did not affect proliferation but inhibited WNT5A-induced apoptosis by 60%. Surface plasmon resonance, siRNA knockdown of FZD5/RYK/FZD8, cell proliferation and apoptosis assays Oncotarget Medium 29930766
2020 YTHDF1 promotes translation of FZD5 mRNA in an m6A-dependent manner in hepatocellular carcinoma cells, functioning as an oncogene through the WNT/β-catenin pathway; multi-omics analysis (translational output profiling) confirmed the translational regulatory mechanism. Multi-omics (ribosome profiling/translational output), m6A methylation analysis, YTHDF1 knockdown/overexpression, in vitro and in vivo functional assays Molecular therapy. Nucleic acids Medium 33230473
2020 FZD5 promotes TNBC cell G1/S transition, DNA replication, DNA damage repair, and stemness; transcription factor FOXM1, which drives BRCA1 and BIRC5 transcription, acts as a downstream effector of FZD5 signaling; Wnt7B was identified as a specific ligand for FZD5 in this context. FZD5 loss- and gain-of-function studies, FOXM1 overexpression rescue experiments, cell cycle and DNA damage repair assays Cell death & disease Medium 33311446
2021 FZD5 knockdown in human mesenchymal stem/stromal cells promotes cellular senescence via non-canonical Wnt pathway regulation; FZD5 overexpression delays cell cycle arrest; WNT5A ligand treatment promotes hMSC proliferation through FZD5. FZD5 siRNA knockdown, FZD5 overexpression, WNT5A ligand treatment, senescence marker assays, proliferation and differentiation assays Stem cells (Dayton, Ohio) Medium 33338299
2021 FZD5 signaling prevents epithelial-mesenchymal transition (EMT) in gastric cancer; PKC links FZD5 to the transcription factor ELF3, which represses ZEB1 to block EMT. FZD5 requires co-receptor LRP5 and WNT7B as a putative ligand. Transcription factors SNAI2 and TEAD1 negatively regulate FZD5 expression (confirmed by ChIP). ChIP-PCR, siRNA knockdown, gene expression analysis (E-cadherin, Vimentin, ZEB1), cell migration and morphology assays, PKC inhibitor, luciferase reporter Cell communication and signaling : CCS Medium 33618713
2021 In cardiac fibroblasts, Wnt5a and Wnt11 promote cardiac fibrosis through FZD5 and EGFR crosstalk: Wnt5a/Wnt11 increased FZD5 expression and EGFR phosphorylation; FZD5 siRNA suppressed p-EGFR levels and fibrotic effects; EGFR knockdown attenuated FZD5, p-p38, and p-ERK levels induced by Wnt5a/Wnt11. TAC mouse model, siRNA knockdown of Wnt5a/Wnt11/EGFR/FZD5, Masson staining for fibrosis, Western blot for signaling intermediates, conditioned medium experiments Cell death & disease Medium 34564708
2022 WNT5A interacts with FZD5 and LRP5 to regulate proliferation and self-renewal of endometrial mesenchymal stem-like cells (eMSC) through WNT/β-catenin signaling; anti-FZD5 antibody neutralization suppressed eMSC clonogenicity and phenotypic expression; FZD5 gene silencing reduced WNT5A binding to eMSC and decreased TCF/LEF transcriptional activity and active β-catenin levels; Dickkopf-1 (LRP antagonist) reduced WNT5A binding and proliferation. Anti-FZD5 neutralizing antibody, FZD5 gene silencing, myometrial cell-eMSC co-culture, TCF/LEF reporter assay, active β-catenin immunostaining, recombinant Dickkopf-1 inhibition Frontiers in cell and developmental biology Medium 35295855
2023 Desert lncRNA HIDEN interacts with RNA-binding protein IMP1 (IGF2BP1) to stabilize FZD5 mRNA; HIDEN depletion reduces the IMP1-FZD5 mRNA interaction and destabilizes FZD5 mRNA, reducing WNT activity and impairing human definitive endoderm differentiation; WNT agonist rescues the differentiation defect caused by HIDEN or IMP1 loss. shRNA/promoter deletion, RNA immunoprecipitation (RIP) of IMP1-FZD5 mRNA interaction, mRNA stability assay, WNT agonist rescue, human PSC differentiation assays Genome biology Medium 37095549
2023 Sfrp2 binds Fzd5 in mesangial cells and promotes Fzd5-induced cytosolic Ca2+ elevation and downstream CaMKII/Mek/Erk pathway activation, leading to mesangial cell proliferation and fibrosis in diabetic kidney disease. snRNA-seq, co-immunoprecipitation (Sfrp2-Fzd5 interaction), Ca2+ concentration measurement, siRNA/overexpression of Sfrp2/Fzd5, Western blot for CaMKII/Mek/Erk, in vivo diabetic mouse model Biochimica et biophysica acta. Molecular basis of disease Medium 37951508
2023 WNT7A-FZD5 signaling axis maintains fallopian tube stem cell renewal: functional approaches and single-cell transcriptomics showed that an endogenously expressed, hormonally regulated WNT7A-FZD5 axis is critical for WNT/β-catenin-dependent stem cell self-renewal. Organoid culture, endogenous WNT/β-catenin reporter engineering, single-cell transcriptomics, bulk transcriptomics, functional loss-of-function approaches Cell reports Medium 37917586
2024 FZD5 is specifically and uniquely upregulated in anterior neural progenitor cells, and this expression is downregulated as cells adopt posterior fate; selective activation of FZD5+LRP6 clustering via a tetravalent bispecific antibody activates WNT/β-catenin signaling in hPSCs and drives midbrain progenitor differentiation, generating functional dopaminergic neurons in vitro and in vivo. FZD receptor surface expression profiling by flow cytometry, tetravalent FZD5/LRP6 bispecific antibody stimulation, hPSC differentiation assays, in vivo dopaminergic neuron functional assessment Development (Cambridge, England) Medium 38358799
2024 DNMT3A binds the FZD5 promoter (by ChIP assay) and suppresses FZD5 transcription via DNA methylation; reduced DNMT3A expression in NSCLC leads to hypomethylation and aberrant FZD5 upregulation; DNMT3A overexpression suppresses FZD5 expression and inhibits lung carcinogenesis in vivo. Chromatin immunoprecipitation (ChIP), quantitative methylation-specific PCR, DNMT3A overexpression in mouse model, FZD5 siRNA knockdown in cell lines and mouse model Heliyon Medium 38707304
2025 Wnt specifically induces FZD5 (and FZD8) endocytosis and degradation in a ZNRF3/RNF43-dependent manner; ZNRF3/RNF43 selectively target FZD5/8 for degradation upon Wnt stimulation; Wnt promotes physical interaction between FZD5 and RNF43; RSPO1 specifically stabilizes FZD5/8 by antagonizing ZNRF3/RNF43; DVL promotes ligand-independent FZD endocytosis but is dispensable for Wnt-induced FZD5/8 degradation. Endocytosis and degradation assays (cell-based), Co-immunoprecipitation (FZD5-RNF43 interaction), ZNRF3/RNF43 knockout and knockdown, RSPO1 treatment, DVL loss-of-function eLife High 41070826
2015 In drug-resistant renal cell carcinoma, miR-124 targets FZD5; Wnt-5a dose-dependently activates FZD5 to stimulate p-PKCα/βII and p-CaMKII; FZD5 silencing reversed PKC/CaMKII activation and suppressed P-glycoprotein expression, demonstrating that FZD5/PKC signaling mediates multi-drug resistance. miR-124 mimic transfection, FZD5 siRNA, Western blot for p-PKCα/βII and p-CaMKII, IC50 assay, flow cytometry apoptosis Tumour biology Low 25861751

Source papers

Stage 0 corpus · 47 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis. Development (Cambridge, England) 270 11092808
2016 Genome-wide CRISPR screens reveal a Wnt-FZD5 signaling circuit as a druggable vulnerability of RNF43-mutant pancreatic tumors. Nature medicine 231 27869803
2018 CircRNA circ_0067934 promotes tumor growth and metastasis in hepatocellular carcinoma through regulation of miR-1324/FZD5/Wnt/β-catenin axis. Biochemical and biophysical research communications 171 29458020
2003 Functional characterization of WNT7A signaling in PC12 cells: interaction with A FZD5 x LRP6 receptor complex and modulation by Dickkopf proteins. The Journal of biological chemistry 120 12857724
2013 A positive feedback loop involving Gcm1 and Fzd5 directs chorionic branching morphogenesis in the placenta. PLoS biology 83 23610556
2020 YTHDF1 Facilitates the Progression of Hepatocellular Carcinoma by Promoting FZD5 mRNA Translation in an m6A-Dependent Manner. Molecular therapy. Nucleic acids 61 33230473
2007 Conserved POU-binding site linked to SP1-binding site within FZD5 promoter: Transcriptional mechanisms of FZD5 in undifferentiated human ES cells, fetal liver/spleen, adult colon, pancreatic islet, and diffuse-type gastric cancer. International journal of oncology 44 17273778
2021 miR-100-5p in human umbilical cord mesenchymal stem cell-derived exosomes mediates eosinophilic inflammation to alleviate atherosclerosis via the FZD5/Wnt/β-catenin pathway. Acta biochimica et biophysica Sinica 43 34254638
2018 FZD5 is a Gαq-coupled receptor that exhibits the functional hallmarks of prototypical GPCRs. Science signaling 43 30514810
2020 FZD5 contributes to TNBC proliferation, DNA damage repair and stemness. Cell death & disease 42 33311446
2021 Down-regulated LINC00115 inhibits prostate cancer cell proliferation and invasion via targeting miR-212-5p/FZD5/Wnt/β-catenin axis. Journal of cellular and molecular medicine 39 34697900
2016 A secreted WNT-ligand-binding domain of FZD5 generated by a frameshift mutation causes autosomal dominant coloboma. Human molecular genetics 36 26908622
2014 Monocyte-secreted Wnt5a interacts with FZD5 in microvascular endothelial cells and induces angiogenesis through tissue factor signaling. Journal of molecular cell biology 35 25240054
2018 Role of WNT5A receptors FZD5 and RYK in prostate cancer cells. Oncotarget 32 29930766
2021 Cardiac Wnt5a and Wnt11 promote fibrosis by the crosstalk of FZD5 and EGFR signaling under pressure overload. Cell death & disease 30 34564708
2015 miR-124 represses FZD5 to attenuate P-glycoprotein-mediated chemo-resistance in renal cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 29 25861751
2021 FZD5 prevents epithelial-mesenchymal transition in gastric cancer. Cell communication and signaling : CCS 28 33618713
2020 FZD5 regulates cellular senescence in human mesenchymal stem/stromal cells. Stem cells (Dayton, Ohio) 27 33338299
2008 Wnt7a interaction with Fzd5 and detection of signaling activation using a split eGFP. Biochemical and biophysical research communications 27 18230341
2018 MiR-212-5p regulates the proliferation and apoptosis of AML cells through targeting FZD5. European review for medical and pharmacological sciences 24 30556883
2009 A coated vesicle-associated kinase of 104 kDa (CVAK104) induces lysosomal degradation of frizzled 5 (Fzd5). The Journal of biological chemistry 23 19643732
2022 WNT5A Interacts With FZD5 and LRP5 to Regulate Proliferation and Self-Renewal of Endometrial Mesenchymal Stem-Like Cells. Frontiers in cell and developmental biology 21 35295855
2018 Endothelial loss of Fzd5 stimulates PKC/Ets1-mediated transcription of Angpt2 and Flt1. Angiogenesis 19 29845518
2017 MiR-99a inhibits keratinocyte proliferation by targeting Frizzled-5 (FZD5) / FZD8 through β-catenin signaling in psoriasis. Die Pharmazie 19 29441905
2023 A desert lncRNA HIDEN regulates human endoderm differentiation via interacting with IMP1 and stabilizing FZD5 mRNA. Genome biology 18 37095549
2021 CircNPM1 strengthens Adriamycin resistance in acute myeloid leukemia by mediating the miR-345-5p/FZD5 pathway. Central-European journal of immunology 17 34764785
2020 Confirmation of FZD5 implication in a cohort of 50 patients with ocular coloboma. European journal of human genetics : EJHG 15 32737437
2021 IgD promotes pannus formation by activating Wnt5A-Fzd5-CTHRC1-NF-κB signaling pathway in FLS of CIA rats and the regulation of IgD-Fc-Ig fusion protein. International immunopharmacology 13 34688134
2021 The fluorescent biosensor for detecting N6 methyladenine FzD5 mRNA and MazF activity. Analytica chimica acta 13 34794576
2023 Sfrp2 promotes renal dysfunction of diabetic kidney disease via modulating Fzd5-induced cytosolic calcium ion concentration and CaMKII/Mek/Erk pathway in mesangial cells. Biochimica et biophysica acta. Molecular basis of disease 12 37951508
2023 Single-cell transcriptomics identifies a WNT7A-FZD5 signaling axis that maintains fallopian tube stem cells in patient-derived organoids. Cell reports 11 37917586
2015 Wnt5a/FZD5/CaMKII signaling pathway mediates the effect of BML-111 on inflammatory reactions in sepsis. International journal of clinical and experimental medicine 11 26770375
2019 Upregulation of FZD5 in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps by Epigenetic Modification. Molecules and cells 8 31082802
2018 MicroRNA-216b actively modulates diabetic angiopathy through inverse regulation on FZD5. Gene 7 29477872
2024 Exploiting spatiotemporal regulation of FZD5 during neural patterning for efficient ventral midbrain specification. Development (Cambridge, England) 6 38358799
2022 Individuals with heterozygous variants in the Wnt-signalling pathway gene FZD5 delineate a phenotype characterized by isolated coloboma and variable expressivity. Ophthalmic genetics 6 36695497
2020 miR-149 regulates the proliferation and apoptosis of human colonic carcinoma cells by targeting FZD5. International journal of clinical and experimental pathology 6 32509059
2016 [Role and action mechanisms of FZD5 in prostate cancer bone metastasis in mice]. Zhonghua nan ke xue = National journal of andrology 5 26939396
2024 circ_0000592 facilitates the progression of esophageal squamous cell carcinoma via miR-155-5p/FZD5 axis. Journal of biochemical and molecular toxicology 4 38780005
2020 Retracted Article: CircBANP acts as a sponge of let-7a to promote gastric cancer progression via the FZD5/Wnt/β-catenin pathway. RSC advances 4 35493872
2024 DNMT3A-mediated DNA methylation and transcription inhibition of FZD5 suppresses lung carcinogenesis. Heliyon 3 38707304
2025 Wnt induces FZD5/8 endocytosis and degradation and the involvement of RSPO-ZNRF3/RNF43 and DVL. bioRxiv : the preprint server for biology 1 39463927
2025 ZNF831-YTHDF1-DNMT1/3a feedback loop regulates lung carcinogenesis and progression through WNT7B-FZD5-β-catenin signalling axis. Free radical biology & medicine 1 40975192
2025 Wnt induces FZD5/8 endocytosis and degradation and the involvement of RSPO-ZNRF3/RNF43 and DVL. eLife 1 41070826
2022 Generation of a BAC transgenic mouse strain that expresses CreERT and a fluorescent protein under the transcriptional control of the Fzd5 locus. Inflammation and regeneration 1 35227325
2023 Age and light damage influence Fzd5 regulation of ocular growth-related genes. Experimental eye research 0 38154732
2021 Retraction: CircBANP acts as a sponge of let-7a to promote gastric cancer progression via the FZD5/Wnt/β-catenin pathway. RSC advances 0 35427047

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