Affinage

FZD10

Frizzled-10 · UniProt Q9ULW2

Length
581 aa
Mass
65.3 kDa
Annotated
2026-06-09
22 papers in source corpus 14 papers cited in narrative 14 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

FZD10 is a Frizzled-family cell-surface Wnt receptor that transduces canonical Wnt/β-catenin signaling and governs cell migration, stemness, and developmental patterning (PMID:15923619, PMID:25406648). At the membrane it binds Wnt7b directly and, in cooperation with the co-receptor LRP5, cooperatively activates canonical β-catenin signaling rather than the non-canonical pathway (PMID:15923619), and it engages the heterotrimeric G protein Gα13 selectively over other Gα subunits to drive YAP/TAZ transcriptional activity upon Wnt stimulation (PMID:28126591). FZD10 expression is set by layered regulation: transcriptionally it is silenced by the BRMS1L–HDAC1 co-repressor complex through H3K9 deacetylation at its promoter, restraining Wnt3–FZD10–β-catenin-driven breast cancer migration and invasion (PMID:25406648); post-transcriptionally its mRNA is stabilized by METTL3-dependent m6A methylation (reversed by FTO/ALKBH5) and destabilized by miR-26b-3p (PMID:30967398, PMID:37728849). In cancer this regulation feeds a FZD10/β-catenin/c-Jun/METTL3 positive-feedback loop that sustains liver cancer stem-cell self-renewal and drug resistance via β-catenin and YAP1 (PMID:36764493), and m6A-driven FZD10 upregulation confers PARP-inhibitor resistance in BRCA-mutated ovarian cancer (PMID:30967398). In development, FZD10 specifically transduces Wnt1 (but not Wnt3a) signaling to expand dorsal neural tube markers in an LRP6-dependent manner (PMID:32531778). FZD10 is internalized upon antibody binding (PMID:18271942) and is packaged into exosomes that transfer the receptor to recipient cells, where it activates ERK1/2 and PI3K signaling (PMID:31349740, PMID:34671555).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2005 Medium

    Established FZD10 as a functional Wnt receptor by showing which ligand it binds and which signaling branch it activates, defining its molecular identity.

    Evidence Cell-surface binding assay and canonical/non-canonical Wnt reporters in transfected cells

    PMID:15923619

    Open questions at the time
    • Co-receptor requirement (LRP5) shown but structural basis of ternary complex undefined
    • Whether other Wnt ligands engage FZD10 not addressed
  2. 2008 Medium

    Demonstrated that surface FZD10 is internalized upon ligand/antibody binding, establishing receptor-mediated internalization and a route for targeting.

    Evidence Antibody (MAb 92-13) binding and internalization assays in synovial sarcoma cells, in vivo imaging

    PMID:18271942

    Open questions at the time
    • Internalization machinery and trafficking fate not dissected
    • Link between internalization and signaling output unaddressed
  3. 2009 Low

    Observed in patient tissue an inverse correlation between FZD10 expression and nuclear β-catenin, raising the question of context-dependent signaling output.

    Evidence Immunohistochemistry on paired colorectal tumor samples (n=104)

    PMID:19134005

    Open questions at the time
    • Correlative only — no manipulation of FZD10
    • Mechanism of the inverse relationship unknown
  4. 2014 High

    Identified transcriptional silencing of FZD10 by the BRMS1L–HDAC1 co-repressor via H3K9 deacetylation, linking epigenetic control of the receptor to Wnt-driven metastasis.

    Evidence ChIP, RNAi knockdown, overexpression, and in vivo xenograft metastasis assays

    PMID:25406648

    Open questions at the time
    • Upstream signals that engage BRMS1L at the FZD10 promoter unknown
    • Generality across non-breast tissues not tested
  5. 2017 Medium

    Defined the transducer downstream of FZD10 by showing selective coupling to Gα13 and resulting YAP/TAZ activation, extending FZD10 beyond β-catenin.

    Evidence Co-IP, dynamic mass redistribution assay, YAP/TAZ reporter, selective G protein co-expression

    PMID:28126591

    Open questions at the time
    • Single-lab Co-IP without reciprocal/structural validation
    • How Gα13 and β-catenin outputs are partitioned not resolved
  6. 2019 High

    Showed FZD10 mRNA is post-transcriptionally controlled by m6A methylation, linking RNA modification to FZD10 protein levels and PARP-inhibitor resistance.

    Evidence m6A-seq, mRNA stability assay, RNAi of FZD10/FTO/ALKBH5, in vivo PARPi sensitivity xenografts

    PMID:30967398

    Open questions at the time
    • m6A reader mediating stabilization not identified
    • Direct site mapping on FZD10 transcript not detailed
  7. 2019 Medium

    Revealed that FZD10 protein and mRNA are exported in exosomes and functionally transferred between cells, proposing a non-cell-autonomous mode of FZD10 action.

    Evidence Exosome isolation, Western blot, RT-PCR, siRNA silencing, viability rescue by exosome re-addition across multiple cancer lines

    PMID:31349740

    Open questions at the time
    • Mechanism of FZD10 sorting into exosomes unknown
    • Whether transferred FZD10 acts as a functional receptor vs cargo unclear
  8. 2020 Medium

    Assigned FZD10 a developmental role by showing it specifically transduces Wnt1 (not Wnt3a) signaling in the dorsal neural tube in an LRP6-dependent manner.

    Evidence Morpholino knockdown and overexpression in Xenopus/chick neural tube, Lrp6 epistasis, in situ hybridization

    PMID:32531778

    Open questions at the time
    • Basis of Wnt1 vs Wnt3a ligand selectivity not defined
    • Mammalian neural-tube relevance not directly tested
  9. 2021 Low

    Linked exosomal FZD10 to proliferative signaling, showing it activates ERK1/2 and Ki-67 in recipient cancer cells.

    Evidence FZD10 siRNA silencing, Western blot for pERK1/2 and Ki-67, exosome re-addition rescue

    PMID:34671555

    Open questions at the time
    • Exosomal FZD10 not isolated as the active species vs other cargo
    • Mechanism connecting FZD10 to ERK1/2 not dissected
  10. 2022 Low

    Extended exosomal FZD10 to angiogenesis, showing PI3K/ERK1/2-dependent (not YAP/TAZ) pro-angiogenic effects on endothelial cells.

    Evidence Exosome isolation, FZD10-siRNA knockdown, tube formation assay, ELISA, Western blot

    PMID:36210708

    Open questions at the time
    • Exosomal FZD10 not directly shown to be the active species
    • How FZD10 selects PI3K/ERK over YAP/TAZ in this context unknown
  11. 2023 High

    Integrated transcriptional, m6A, and downstream outputs into a FZD10/β-catenin/c-Jun/METTL3 feedback loop driving liver cancer stem-cell self-renewal and lenvatinib resistance.

    Evidence RNA-seq, RIP, luciferase, patient-derived organoids/xenografts, AAV-mediated FZD10 knockdown

    PMID:36764493

    Open questions at the time
    • How c-Jun engages the METTL3 promoter mechanistically not fully resolved
    • Generality of the loop beyond liver CSCs untested
  12. 2023 Medium

    Identified miR-26b-3p as a direct destabilizer of FZD10 mRNA and tied FZD10/GSK3β/β-catenin signaling to enteric glial survival and intestinal motility.

    Evidence Luciferase target validation, FZD10 siRNA, Western blot, apoptosis flow cytometry, in vivo antagomir rescue

    PMID:37728849

    Open questions at the time
    • Single-lab; broader miRNA network on FZD10 not mapped
    • Receptor-level signaling events upstream of GSK3β in EGCs not detailed
  13. 2026 Low

    Implicated the transcription factor E2F2 as an activator of FZD10 expression sustaining arsenic-induced breast cancer stem-like properties via Wnt/β-catenin.

    Evidence Transcriptomic profiling and E2F2/FZD10 manipulation with Wnt/β-catenin readouts

    PMID:41672294

    Open questions at the time
    • Direct E2F2 binding to the FZD10 promoter (e.g., ChIP) not demonstrated
    • Single lab, single carcinogen context

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FZD10's distinct outputs (canonical β-catenin, Gα13–YAP/TAZ, and exosomal ERK/PI3K) are selected in a given cell, and the structural basis of its Wnt-ligand and co-receptor selectivity, remain unresolved.
  • No structural model of FZD10–Wnt–LRP complexes
  • Determinants partitioning β-catenin vs YAP/TAZ vs exosomal signaling unknown
  • Mechanism of FZD10 sorting into exosomes uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 2 GO:0048018 receptor ligand activity 1
Localization
GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-1266738 Developmental Biology 1
Partners
GNA13LRP5LRP6WNT1WNT7B

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Wnt7b binds directly to FZD10 (and FZD1) on the cell surface and cooperatively activates canonical Wnt/β-catenin signaling in the presence of the co-receptor LRP5, but does not activate the non-canonical Wnt pathway through this interaction. Cell surface binding assay, cell transfection with canonical and non-canonical Wnt pathway reporters, biochemical binding analysis Molecular and cellular biology Medium 15923619
2008 FZD10 protein is expressed on the cell surface of synovial sarcoma cells and is efficiently internalized following binding of an anti-FZD10 monoclonal antibody (MAb 92-13), demonstrating receptor-mediated internalization capacity. Cell binding assay, in vivo fluorescent imaging, radioisotope tracking, immunohistochemistry Cancer science Medium 18271942
2008 In colorectal cancer tissues, FZD10-immunopositive cancer cells show significantly reduced nuclear accumulation of β-catenin compared to FZD10-negative cells, indicating an inverse correlation between FZD10 expression and canonical Wnt/β-catenin nuclear signaling. Immunohistochemistry on paired tumor samples (n=104 patients) Cancer science Low 19134005
2014 BRMS1L, a component of the Sin3A-HDAC co-repressor complex, epigenetically silences FZD10 transcription by recruiting HDAC1 and inducing histone H3K9 deacetylation at the FZD10 promoter, thereby inhibiting WNT3-FZD10-β-catenin signaling and breast cancer cell migration and invasion. ChIP assay (HDAC1 recruitment and H3K9 deacetylation at FZD10 promoter), RNAi knockdown, overexpression, in vivo xenograft metastasis assay Nature communications High 25406648
2017 FZD10 interacts with and signals through the heterotrimeric G protein Gα13 (but not Gα12, Gαi1, GαoA, Gαs, or Gαq); WNT stimulation induces dissociation of Gα13 from FZD10 and leads to Gα12/13-dependent cell changes; FZD10-mediated Gα13 activation drives YAP/TAZ transcriptional activity. Co-immunoprecipitation, dynamic mass redistribution (DMR) assay, YAP/TAZ transcriptional reporter assay, selective G protein co-expression experiments Cellular signalling Medium 28126591
2019 m6A modification of FZD10 mRNA (mediated by METTL3 and reversible by FTO/ALKBH5 demethylases) increases FZD10 mRNA stability, upregulates FZD10 protein, and activates the Wnt/β-catenin pathway to promote PARP inhibitor resistance in BRCA-mutated ovarian cancer cells. Global m6A profiling, m6A-seq, mRNA stability assay, RNAi knockdown of FZD10/FTO/ALKBH5, in vitro and in vivo xenograft PARPi sensitivity assays Cancer research High 30967398
2019 FZD10 protein and FZD10 mRNA are packaged into exosomes secreted by colorectal, gastric, hepatic, and cholangio cancer cell lines; exosomal FZD10 can be transferred to silenced recipient cells, restoring FZD10 levels and cell viability. Exosome isolation, Western blot, RT-PCR, siRNA silencing, cell viability assay with exosome re-addition Cells Medium 31349740
2020 FZD10 is required for Wnt1-induced ventral expansion of dorsal neural tube markers (Pax6, Pax7) in the developing spinal cord; FZD10 knockdown blocks Wnt1-mediated effects but not Wnt3a-mediated dorsalization; co-expression of the co-receptor Lrp6 dramatically enhances Wnt1/FZD10-dependent activation of dorsal markers. Morpholino knockdown in Xenopus/chick neural tube, gain-of-function overexpression, Lrp6 co-expression epistasis experiments, in situ hybridization for dorsal marker expression PloS one Medium 32531778
2020 Exosomes derived from metastatic colon cancer cells deliver FZD10 protein to normal colonic epithelial cells (HCEC-1CT), inducing epithelial-mesenchymal transition (EMT) as evidenced by acquisition of mesenchymal markers and migration capability. Exosome isolation and transfer, immunofluorescence for EMT markers, migration assay (scratch test) International journal of molecular sciences Low 32933173
2021 Exosome-released FZD10 from colorectal and gastric cancer cells increases Ki-67 expression via phospho-ERK1/2 (MAPK3); FZD10 silencing reduces pERK1/2 and Ki-67, while addition of exogenous exosomes partially restores their expression. FZD10 siRNA silencing, Western blot for pERK1/2 and Ki-67, exosome re-addition rescue experiment Frontiers in oncology Low 34671555
2022 Exosomal FZD10 derived from NSCLC cells promotes HUVEC tube formation and upregulates VEGFA and Ang-1 in vitro; this pro-angiogenic effect is dependent on activation of PI3K and ERK1/2 signaling pathways (but not YAP/TAZ), as demonstrated by FZD10 knockdown experiments. Exosome isolation, FZD10-siRNA knockdown, in vitro tube formation assay, ELISA (VEGFA, Ang-1), Western blot (PI3K, pERK1/2, YAP/TAZ) Nan fang yi ke da xue xue bao Low 36210708
2023 METTL3-dependent m6A methylation of FZD10 mRNA activates FZD10 expression in liver cancer stem cells (CSCs); FZD10 promotes CSC self-renewal and lenvatinib resistance via activation of β-catenin and YAP1; a FZD10-β-catenin/c-Jun axis transcriptionally activates METTL3, forming a positive feedback loop; and the FZD10/β-catenin/c-Jun/MEK/ERK axis determines lenvatinib response. RNA-seq, RNA-binding protein immunoprecipitation (RIP), luciferase reporter assay, in vitro and in vivo functional studies, patient-derived tumor organoids, patient-derived xenografts, AAV-mediated FZD10 knockdown Gastroenterology High 36764493
2023 miR-26b-3p directly targets FZD10 mRNA (validated by luciferase assay); FZD10 downregulation increases GSK3β phosphorylation, decreases β-catenin, and promotes enteric glial cell (EGC) apoptosis; miR-26b-3p antagomir relieves intestinal dysmotility in vivo by restoring FZD10/GSK3β/β-catenin signaling in EGCs. Luciferase reporter assay (miR-26b-3p/FZD10 targeting), siRNA knockdown of FZD10, Western blot (p-GSK3β, β-catenin), flow cytometry (apoptosis), in vivo mouse model (loperamide-induced constipation) with miR-26b-3p antagomir Molecular neurobiology Medium 37728849
2026 The transcription factor E2F2 directly regulates FZD10 expression; E2F2/FZD10 axis activates the Wnt/β-catenin pathway to sustain breast cancer stem cell-like properties induced by chronic arsenic exposure in mammary epithelial cells. Transcriptomic profiling, functional studies with E2F2 and FZD10 manipulation, Wnt/β-catenin pathway readouts Food and chemical toxicology Low 41672294

Source papers

Stage 0 corpus · 22 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2023 N6-Methyladenosine-Mediated Up-Regulation of FZD10 Regulates Liver Cancer Stem Cells' Properties and Lenvatinib Resistance Through WNT/β-Catenin and Hippo Signaling Pathways. Gastroenterology 235 36764493
2005 Wnt7b activates canonical signaling in epithelial and vascular smooth muscle cells through interactions with Fzd1, Fzd10, and LRP5. Molecular and cellular biology 159 15923619
2019 N6-Methylation of Adenosine of FZD10 mRNA Contributes to PARP Inhibitor Resistance. Cancer research 146 30967398
2014 BRMS1L suppresses breast cancer metastasis by inducing epigenetic silence of FZD10. Nature communications 94 25406648
2008 Radioimmunotherapy of human synovial sarcoma using a monoclonal antibody against FZD10. Cancer science 63 18271942
2002 Up-regulation of Frizzled-10 (FZD10) by beta-estradiol in MCF-7 cells and by retinoic acid in NT2 cells. International journal of oncology 58 11743650
2019 FZD10 Carried by Exosomes Sustains Cancer Cell Proliferation. Cells 38 31349740
2008 Inverse correlation of the up-regulation of FZD10 expression and the activation of beta-catenin in synchronous colorectal tumors. Cancer science 37 19134005
2017 FZD10-Gα13 signalling axis points to a role of FZD10 in CNS angiogenesis. Cellular signalling 30 28126591
2020 A Possible Role of FZD10 Delivering Exosomes Derived from Colon Cancers Cell Lines in Inducing Activation of Epithelial-Mesenchymal Transition in Normal Colon Epithelial Cell Line. International journal of molecular sciences 25 32933173
2021 FZD10-targeted α-radioimmunotherapy with 225 Ac-labeled OTSA101 achieves complete remission in a synovial sarcoma model. Cancer science 24 34935247
2021 Exosome Released FZD10 Increases Ki-67 Expression via Phospho-ERK1/2 in Colorectal and Gastric Cancer. Frontiers in oncology 19 34671555
2020 Effectiveness of a Controlled 5-FU Delivery Based on FZD10 Antibody-Conjugated Liposomes in Colorectal Cancer In vitro Models. Pharmaceutics 18 32664186
2009 Radioimmunotherapy of solid tumors targeting a cell-surface protein, FZD10: therapeutic efficacy largely depends on radiosensitivity. Annals of nuclear medicine 17 19412654
2020 FZD10 regulates cell proliferation and mediates Wnt1 induced neurogenesis in the developing spinal cord. PloS one 16 32531778
2020 SEPT9_v2, frequently silenced by promoter hypermethylation, exerts anti-tumor functions through inactivation of Wnt/β-catenin signaling pathway via miR92b-3p/FZD10 in nasopharyngeal carcinoma cells. Clinical epigenetics 12 32138771
2024 Repurposing FDA-approved drugs targeting FZD10 in nasopharyngeal carcinoma: insights from molecular dynamics simulations and experimental validation. Scientific reports 7 39733096
2023 MiR-26b-3p Promotes Intestinal Motility Disorder by Targeting FZD10 to Inhibit GSK3β/β-Catenin Signaling and Induce Enteric Glial Cell Apoptosis. Molecular neurobiology 7 37728849
2023 Transcriptomic profiling revealed FZD10 as a novel biomarker for nasopharyngeal carcinoma recurrence. Frontiers in oncology 6 36776376
2022 [Exosomal FZD10 derived from non-small cell lung cancer cells promotes angiogenesis of human umbilical venous endothelial cells in vitro]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 1 36210708
2026 Arsenic exposure induces stemness in human normal breast epithelial cells via the E2F2/FZD10 axis. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 0 41672294
2025 Development of immune radiotherapy with yttrium by targeting Frizzled homologue 10 (FZD10) in cervical cancer. Gynecologic oncology reports 0 40958973

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