Affinage

SFRP1

Secreted frizzled-related protein 1 · UniProt Q8N474

Length
314 aa
Mass
35.4 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SFRP1 is a secreted Wnt antagonist that controls cell fate, proliferation, and tissue homeostasis across numerous developmental and adult contexts by modulating both canonical and non-canonical Wnt signaling, as well as Wnt-independent pathways. As a secreted glycoprotein, SFRP1 directly binds Wnt ligands upstream of GSK-3 to inhibit β-catenin accumulation (PMID:16425220), and independently engages Frizzled-2 receptors to guide axon growth through Gα-protein and cyclic nucleotide signaling (PMID:16172602); at low concentrations it activates the Wnt/PCP-Rac1 pathway in dopaminergic neurons (PMID:22290867) and restrains Wnt/PCP-JNK signaling in kidney and heart (PMID:25253698, PMID:30377735). SFRP1 is transcriptionally regulated by Hedgehog-Gli (PMID:17035233), SOX2 (PMID:33107226), and oncogenic AKT1-E17K (PMID:24096618), and is frequently epigenetically silenced through promoter DNA methylation mediated by DNMT1/HDAC1 or DNMT3b recruitment (by HCV core protein or HOTTIP lncRNA) and by EZH2-dependent histone methylation (PMID:23770846, PMID:31902746, PMID:21515604). Functionally, SFRP1 mediates cellular senescence via Wnt inhibition and Rb pathway activation (PMID:22927647), maintains stem cell quiescence in hair follicles and the neural subventricular zone (PMID:35689817, PMID:35210419), regulates trophoblast differentiation and somitogenesis through redundancy with other SFRPs (PMID:33109217, PMID:16467359), and when packaged into fibroblast-derived extracellular vesicles paradoxically promotes lung fibrosis by activating WNT/β-catenin in alveolar epithelial cells (PMID:39315549).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2003 High

    Establishing that SFRP1 modulates retinal cell fate and protects against apoptosis through β-catenin-independent mechanisms resolved that its function extends beyond simple canonical Wnt antagonism.

    Evidence Retroviral overexpression in chick retinal cultures with β-catenin/TCF reporters showing no change in canonical activity, plus GSK3β phosphorylation analysis; parallel ceramide-induced apoptosis assays with antisense inhibition and recombinant protein in fibroblasts

    PMID:12724355 PMID:14581477

    Open questions at the time
    • Identity of the β-catenin-independent downstream effector in retinal progenitors not established
    • Whether anti-apoptotic activity requires Wnt binding or a separate receptor interaction unknown
  2. 2005 High

    Demonstrating that SFRP1 directly binds Frizzled-2 and signals through Gα proteins independently of Wnt inhibition established a receptor-mediated signaling mode for a secreted Wnt antagonist.

    Evidence Co-immunoprecipitation of SFRP1 with Fz2, dominant-negative Fz2 abolishes growth cone responses, pharmacological Gα and cyclic nucleotide manipulation in retinal ganglion cell axon assays

    PMID:16172602

    Open questions at the time
    • Structural basis of SFRP1-Fz2 interaction not resolved
    • Whether Fz2-dependent signaling operates outside retinal neurons unknown
  3. 2006 High

    Three advances placed SFRP1 mechanistically: its site of Wnt pathway inhibition was mapped upstream of GSK-3 via epistasis, its transcription was shown to be directly driven by Hedgehog-Gli factors linking two major morphogen pathways, and compound knockouts revealed functional redundancy with SFRP2 in somitogenesis and Notch clock regulation.

    Evidence Purified recombinant SFRP1 blocking Wnt-3a but not LiCl-induced β-catenin; ChIP showing Gli1 at the SFRP1 promoter with siRNA rescue; Sfrp1/Sfrp2 double-KO mice with altered Lfng/Hes7 oscillations

    PMID:16425220 PMID:16467359 PMID:17035233

    Open questions at the time
    • Whether SFRP1 sequesters Wnt ligands or competes for Frizzled binding to achieve upstream inhibition not distinguished
    • Mechanism by which SFRP1 loss alters Notch oscillation timing unclear
  4. 2008 High

    In vivo gain-of-function in the trabecular meshwork showed SFRP1 reduces aqueous outflow and raises intraocular pressure through Wnt/β-catenin suppression, establishing a physiological role in IOP regulation.

    Evidence Adenoviral SFRP1 overexpression in mouse eyes with dose-dependent IOP increase reversible by downstream Wnt inhibitor; ex vivo human eye perfusion

    PMID:18274669

    Open questions at the time
    • Endogenous regulation of SFRP1 levels in glaucomatous TM not mechanistically defined
    • Whether other SFRPs contribute redundantly in TM unknown
  5. 2009 Medium

    Loss-of-function studies in mammary epithelial cells and hematopoietic stem cells revealed that SFRP1 restrains β-catenin-driven EMT/stemness and limits HSC self-renewal, defining its tumor-suppressive and stem cell regulatory functions.

    Evidence shRNA knockdown in 76N TERT cells elevating nuclear β-catenin, Cyclin D1, CD44high/CD24low population; recombinant SFRP1 reducing multipotent progenitors and long-term HSC repopulation in competitive transplantation

    PMID:19422694 PMID:19778523

    Open questions at the time
    • Whether SFRP1 effects on HSC are cell-autonomous or niche-mediated not resolved
    • Downstream targets of β-catenin mediating CD44/CD24 switch not identified
  6. 2011 Medium

    Discovery that EZH2 epigenetically silences SFRP1 via H3K27 trimethylation at its promoter in rheumatoid arthritis fibroblasts established a histone modification-based mechanism for SFRP1 repression in disease.

    Evidence ChIP for histone marks at the SFRP1 promoter, EZH2 overexpression/siRNA in RA synovial fibroblasts, TNF-α induction via NF-κB/JNK

    PMID:21515604

    Open questions at the time
    • Whether EZH2-mediated SFRP1 silencing occurs in cancers beyond RA fibroblasts not tested here
    • Quantitative relationship between H3K27me3 density and SFRP1 repression not defined
  7. 2012 High

    Three studies collectively established that SFRP1 mediates cellular senescence through Wnt inhibition and Rb pathway activation, promotes Th17 differentiation via TGF-β/Smad2/3 enhancement, and activates Wnt/PCP-Rac1 signaling in dopaminergic neuron development—revealing context-dependent pathway selection.

    Evidence Senescence assays with gain/loss-of-function and cancer mutant analysis; recombinant SFRP1 with TGF-β blocking epistasis during Th17 polarization; Sfrp1/Sfrp2 double-KO mice phenocopying Wnt5a-/- with Rac1 pathway activation

    PMID:22290867 PMID:22740051 PMID:22927647

    Open questions at the time
    • How SFRP1 selectively activates PCP versus inhibiting canonical Wnt in different cell types not explained
    • Whether Th17-promoting activity is Wnt-dependent or a direct TGF-β pathway effect unresolved
  8. 2013 High

    Multiple studies converged on SFRP1 as a target of epigenetic silencing (DNMT1/HDAC1 by HCV core protein, promoter methylation in systemic sclerosis) and transcriptional regulation (SOX2 in cancer-associated fibroblasts, miR-328, AKT1-E17K), establishing the diverse upstream control mechanisms that modulate SFRP1 expression in disease.

    Evidence ChIP demonstrating DNMT1/HDAC1 recruitment to SFRP1 promoter by HCV core with bisulfite sequencing and xenograft rescue; 5-aza reactivation of SFRP1 in SSc fibroblasts; ChIP-seq for SOX2 at Sfrp1 promoter in CAFs; 3'UTR luciferase assay for miR-328; AKT1-E17K transfection with immunohistochemistry in meningiomas

    PMID:23698475 PMID:23770846 PMID:24096618 PMID:24305703 PMID:33107226

    Open questions at the time
    • Relative contribution of DNA methylation versus histone modification to SFRP1 silencing in any single disease context not quantified
    • Whether SOX2-driven SFRP1 in CAFs acts via canonical or non-canonical Wnt on tumor cells unresolved
  9. 2014 High

    Sfrp1 knockout in obstructive nephropathy demonstrated that SFRP1 specifically restrains non-canonical Wnt/PCP-JNK signaling and EMT in kidney, without affecting canonical Wnt levels, clarifying pathway selectivity in a fibrotic context.

    Evidence Sfrp1 KO mouse UUO model with Western blot dissection of canonical versus JNK/c-Jun pathways, EMT markers, and apoptosis

    PMID:25253698

    Open questions at the time
    • Whether SFRP1 directly binds Wnt5a or another non-canonical Wnt to suppress PCP-JNK not determined
    • Applicability to other organ fibrosis models not tested
  10. 2019 Medium

    HOTTIP lncRNA was shown to recruit DNMT3b to the SFRP1 promoter for methylation-mediated silencing, and SFRP1 was identified as an epigenetic gatekeeper maintaining periodontal ligament progenitor identity via H3K4me3 marks, expanding the repertoire of epigenetic regulators converging on SFRP1.

    Evidence RNA pull-down and RIP for HOTTIP-DNMT3b interaction, ChIP and bisulfite sequencing at SFRP1 promoter in RA fibroblasts; ChIP for H3K4me3/H3K27me3 comparing PDL versus alveolar bone progenitors with WAY-316606 inhibitor

    PMID:31215318 PMID:31902746

    Open questions at the time
    • Whether HOTTIP-DNMT3b mechanism operates in tissues beyond RA synovium unknown
    • Whether SFRP1-dependent mineralization suppression requires canonical Wnt inhibition specifically not tested
  11. 2020 Medium

    Sfrp1/Sfrp5 double knockout revealed that SFRP1 restrains canonical Wnt-β-catenin to prevent premature trophoblast differentiation and giant cell overproduction, acting through Ascl2 repression.

    Evidence Double-KO mice and trophoblast-specific β-catenin gain-of-function model converging on Ascl2 downregulation

    PMID:33109217

    Open questions at the time
    • Individual contribution of SFRP1 versus SFRP5 not separable due to redundancy
    • Whether Ascl2 is a direct or indirect Wnt target in trophoblasts unresolved
  12. 2021 Medium

    SFRP1 was identified as an astrocyte-derived amplifier of microglial neuroinflammation acting through the HIF pathway, establishing a paracrine non-Wnt signaling role in the CNS.

    Evidence SFRP1 KO/overexpression in mouse neuroinflammation models with HIF pathway gene expression and conditioned medium experiments

    PMID:34569685

    Open questions at the time
    • Whether SFRP1 directly activates HIF signaling or acts through intermediate Wnt-dependent steps unclear
    • Receptor on microglia mediating SFRP1 response not identified
  13. 2022 Medium

    SFRP1 was shown to maintain quiescence of hair follicle stem cells and adult neural stem cells; its loss depletes HFSCs via a BMP-AKT-GSK3β cross-talk mechanism and its pharmacological inhibition activates human SVZ neural progenitors.

    Evidence Sfrp1 KO mice with HFSC flow cytometry and BMP/GSK3β inhibitor epistasis; WAY-316606 administration in vivo with scRNA-seq of human SVZ

    PMID:35210419 PMID:35689817

    Open questions at the time
    • Whether SFRP1 maintains quiescence solely through canonical Wnt suppression or additional pathways in each stem cell niche unresolved
    • Long-term consequences of pharmacological SFRP1 inhibition on stem cell exhaustion not assessed
  14. 2024 High

    Two studies established SFRP1 as a context-dependent modulator of lung fibrosis: it restrains TGFβ1-driven fibroblast-to-myofibroblast transition via RHOA, yet when packaged in fibroblast-derived extracellular vesicles it paradoxically activates WNT/β-catenin in alveolar epithelial cells to promote fibrosis.

    Evidence scRNA-seq, spatial transcriptomics, and genetic lineage tracing of fibroblast transitions with SFRP1 loss-of-function; label-free proteomics of BALF-EVs with Sfrp1 KO bleomycin model and β-catenin/Krt8 readouts in precision-cut lung slices

    PMID:38212077 PMID:39315549

    Open questions at the time
    • How vesicular SFRP1 activates rather than inhibits Wnt/β-catenin in recipient alveolar cells remains mechanistically unexplained
    • Whether the fibroblast-intrinsic and EV-mediated roles are simultaneously operative in human IPF not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SFRP1 switches between canonical Wnt antagonism, PCP pathway activation, and Frizzled-dependent Wnt-independent signaling in different cellular contexts remains the central unresolved question.
  • No structural model of SFRP1 bound to Wnt ligands versus Frizzled receptors
  • Concentration-dependent pathway switching mechanism not reconstituted
  • How vesicular versus soluble SFRP1 achieves opposite effects on β-catenin not explained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0048018 receptor ligand activity 3
Localization
GO:0005576 extracellular region 7 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 11 R-HSA-1266738 Developmental Biology 4 R-HSA-4839726 Chromatin organization 4 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2
Partners
DNMT1EZH2FZD2HDAC1PARP1SFRP2SOX2WNT3A

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 SFRP1 directly binds Frizzled-2 (Fz2) receptor and guides retinal ganglion cell axon growth through a Wnt-inhibition-independent mechanism requiring Gα protein activation, protein synthesis/degradation, and modulation by cyclic nucleotide levels; interference with Fz2 expression abolishes growth cone responses to SFRP1. Chick and Xenopus retinal ganglion cell axon growth assays, co-immunoprecipitation of SFRP1 with Fz2, dominant-negative receptor interference, pharmacological manipulation of Gα proteins and cyclic nucleotides Nature neuroscience High 16172602
2003 SFRP1 promotes retinal ganglion cell and cone photoreceptor generation while decreasing amacrine cell numbers via a β-catenin-independent mechanism involving phosphorylation-dependent inhibition of GSK3β; SFRP1 does not modify basal β-catenin transcriptional activity in retinal cells. Retroviral overexpression in chick retinal cultures, β-catenin/TCF luciferase reporter assay, dominant-negative GSK3β phenocopy, Western blot for pGSK3β Journal of cell science High 12724355
2006 Sfrp1 and Sfrp2 directly interact with Wnt ligands to inhibit Wnt-3a-induced β-catenin accumulation in a GSK-3-dependent manner (they cannot block LiCl-induced β-catenin accumulation), demonstrating their site of action is upstream of GSK-3. In vitro Wnt-3a inhibition assay in L cells, LiCl epistasis experiment, purified recombinant Sfrp proteins Developmental dynamics High 16425220
2006 Gli1 and Gli2 transcription factors of the Hedgehog signaling pathway directly regulate sFRP1 transcription; chromatin immunoprecipitation demonstrates Gli1 binds the sFRP1 promoter, and sFRP1 in turn suppresses Wnt-1-mediated β-catenin accumulation, establishing sFRP1 as a mechanistic link between Hh and Wnt pathway cross-talk. ChIP assay, ectopic Gli1 expression in gastric cancer cells, SMO antagonist (KAAD-cyclopamine) treatment, β-catenin accumulation assay, sFRP1 siRNA rescue Journal of biological chemistry High 17035233
2006 Sfrp1 and Sfrp2 double knockout mice display anterior-posterior axis shortening and abnormal somite segmentation associated with altered Notch signaling oscillations (Lfng and Hes7 expression); single knockouts have no phenotype, indicating functional redundancy. Aberrant presomitic mesoderm cell migration also contributes. Mouse double-knockout genetics, in situ hybridization for segmentation clock genes (Lfng, Hes7), histological analysis of somites Development High 16467359
2008 Elevated sFRP1 in the trabecular meshwork (TM) inhibits Wnt signaling (reduces β-catenin) and decreases aqueous outflow facility, causing elevated intraocular pressure; adenoviral overexpression of sFRP1 in mouse eyes increases IOP in a titer-dependent manner reversible by a downstream Wnt signaling inhibitor. Ex vivo human eye perfusion culture with recombinant sFRP1, intravitreal adenoviral injection in mice, IOP measurement, β-catenin immunostaining in TM Journal of clinical investigation High 18274669
2012 SFRP1 is oversecreted upon cellular senescence (DNA damage or oxidative stress) and is both necessary and sufficient for senescence induction; it acts through inhibition of Wnt signaling and activation of the retinoblastoma (Rb) pathway; cancer-associated SFRP1 mutants are defective for senescence induction. Knockdown and overexpression in human cells, stress-induced senescence assays (SA-β-gal, growth arrest), Rb pathway analysis, cancer mutant functional testing Molecular and cellular biology High 22927647
2012 SFRP1 and SFRP2 activate the Wnt/planar-cell-polarity (PCP)/Rac1 pathway in dopaminergic neurons; compound Sfrp1/Sfrp2 double knockout mice display a Wnt/PCP phenotype (AP shortening of VM, lateral expansion of Shh domain, accumulation of Nurr1+ precursors) similar to Wnt5a-/- mice; low/medium concentrations of sFRP1 promote DA differentiation mimicking Wnt5a. Sfrp1/Sfrp2 compound knockout mouse genetics, primary VM cultures, embryonic stem cell differentiation assays, Rac1 pathway activation assays Stem cells High 22290867
2014 Sfrp1 deficiency in a mouse model of obstructive nephropathy increases myofibroblast markers (αSMA), promotes epithelial-to-mesenchymal transition (decreased E-cadherin, increased vimentin), and elevates phospho-c-Jun/JNK (non-canonical Wnt/PCP pathway) without affecting canonical Wnt signaling levels; also increases apoptosis in obstructed kidneys. Sfrp1 knockout mouse UUO model, Western blot for EMT markers and JNK/pJNK, histology, TUNEL apoptosis assay Journal of biological chemistry High 25253698
2003 SFRP1 protects fibroblasts from ceramide-induced apoptosis by regulating p53, caspase-3, caspase-9, and BIK expression; inhibition of endogenous SFRP1 increases cell death while exogenous SFRP1 reduces apoptosis in vitro and in vivo. Antisense inhibition and exogenous recombinant protein treatment in PDL and gingival fibroblasts, apoptosis assays (TUNEL, caspase activity), in vivo dermal fibroblast model Journal of biological chemistry Medium 14581477
2005 SFRP1 treatment of prostatic epithelial cells increases proliferation, decreases apoptosis, and decreases canonical Wnt/β-catenin signaling; SFRP1 treatment of developing prostates in culture increases organ growth, suggesting a paracrine role from tumor stroma promoting epithelial proliferation. Recombinant SFRP1 treatment of prostatic epithelial cell lines and organ culture, proliferation assays, apoptosis assays, β-catenin signaling readout, in vivo proliferation Cancer research Medium 16288033
2009 SFRP1 knockdown in non-malignant mammary epithelial cells raises nuclear β-catenin, activates Wnt signaling, increases Cyclin D1, promotes partial EMT, confers resistance to anoikis, increases migration and invasion, and generates a CD44high/CD24low population. shRNA knockdown in 76N TERT cells, β-catenin fractionation, invasion/migration assays, flow cytometry for CD44/CD24 markers, anchorage-independent growth assay Cancer cell international Medium 19422694
2011 EZH2 (histone methyltransferase) is overexpressed in rheumatoid arthritis synovial fibroblasts, is induced by TNF-α via NF-κB and JNK pathways, and epigenetically silences SFRP1 by histone methylation at its promoter; SFRP1 promoter occupation by activating vs. silencing histone marks correlates with expression levels. ChIP assay for histone marks at SFRP1 promoter, EZH2 overexpression and siRNA knockdown, qRT-PCR, Western blot, kinase inhibitor experiments, reporter assays Annals of the rheumatic diseases Medium 21515604
2013 HCV core protein silences SFRP1 by recruiting DNMT1 and HDAC1 to the SFRP1 promoter, causing CpG hypermethylation and repression of acetyl-H3 binding; SFRP1 silencing activates Wnt/β-catenin (c-Myc, cyclin D1) and induces EMT; restoring SFRP1 or knocking down DNMT1 reverses these effects in vivo and in vitro. ChIP for DNMT1, HDAC1, acetyl-H3 at SFRP1 promoter; bisulfite sequencing; DNMT1 knockdown; SFRP1 overexpression; xenograft mouse model; Western blot for EMT markers and β-catenin targets Oncogene High 23770846
2019 SFRP1 maintains the non-mineralized state of periodontal ligament (PDL) progenitors; SFRP1 promoter carries H3K4me3 active marks in PDL fibroblasts but not in alveolar bone progenitors; inhibition or knockdown of SFRP1 promotes PDL mineralization and activates RUNX2/SP7 via H3K4me3-mediated transcription. ChIP for H3K4me3/H3K27me3, small molecule inhibitor (WAY-316606), siRNA knockdown, mineralization assays, Western blot in PDL vs AB progenitors Stem cells and development Medium 31215318
2012 sFRP1 promotes human Th17 cell differentiation by enhancing TGF-β/Smad2/3 phosphorylation in CD4+ T cells; blocking TGF-β signaling abolishes the Th17-promoting activity of sFRP1. Recombinant sFRP1 addition during TCR-mediated stimulation and Th17-differentiation conditions, IL-17 ELISA, phospho-Smad2/3 Western blot, TGF-β blocking antibody epistasis European journal of immunology Medium 22740051
2008 Recombinant Sfrp1 or Sfrp2 inhibit myoblast differentiation (myotube formation) without affecting cell cycle or apoptosis; cells must be treated during proliferation for maximal effect, and removing Sfrp restores normal differentiation. Recombinant protein treatment of C2C12 and primary satellite cell cultures, myotube counting, cell cycle analysis, apoptosis assays, washout experiment Cell and tissue research Medium 18322704
2013 SFRP1 is a direct target of miR-328 (validated by 3'UTR luciferase assay); miR-328 downregulates SFRP1 protein and activates Wnt signaling to promote glioma cell invasion. 3'UTR luciferase reporter assay, miRNA mimic/inhibitor transfection, TCF/LEF reporter assay, Western blot for SFRP1, invasion assay Neuro-oncology Medium 24305703
2013 SOX2 directly binds Sfrp1/2 promoters in cancer-associated fibroblasts (CAFs) to drive their expression; inactivation of Sox2 or Sfrp1/2 in CAFs impairs induction of migration and invasion of colon cancer cells and reduces tumorigenicity in vivo. PKCζ deficiency generates this SOX2-dependent CAF population. ChIP-seq/ChIP for SOX2 at Sfrp1/2 promoters, Sox2/Sfrp1/2 KO in CAFs, coculture migration/invasion assays, in vivo tumorigenicity Developmental cell High 33207226
2024 SFRP1 modulates TGFβ1-induced lung fibroblast invasion and RHOA pathway activity; TGFβ1 downregulates SFRP1 in transitional fibroblasts and switches them to an invasive CTHRC1+ myofibroblast identity; loss-of-function studies confirm SFRP1 restrains this transition. Single-cell RNA-seq, spatial transcriptomics, genetic lineage tracing, TGFβ1 treatment, SFRP1 loss-of-function invasion assays, RHOA pathway readout European respiratory journal High 38212077
2024 Fibroblast-derived extracellular vesicles are enriched in SFRP1; vesicular SFRP1 promotes lung fibrosis by increasing WNT/β-catenin signaling and transitional cell markers (keratin 8) in alveolar type 2 cells; Sfrp1 deficiency inhibits the pro-fibrotic activity of fibroblast-derived EVs in vivo. Label-free proteomics of BALF-EVs, Sfrp1 KO mouse bleomycin fibrosis model, precision-cut lung slice assays, Western blot for β-catenin and Krt8 JCI insight High 39315549
2021 SFRP1 (largely astrocyte-derived) promotes and sustains microglial activation in neuroinflammation by upregulating components of the HIF-dependent inflammatory pathway and, to a lesser extent, NF-κB pathway; SFRP1 acts as an astrocyte-to-microglia amplifier of neuroinflammation. Mouse models of acute and chronic neuroinflammation, SFRP1 modulation (KO/overexpression), HIF pathway gene expression analysis, NF-κB readouts, astrocyte-conditioned medium experiments EMBO reports Medium 34569685
2015 SFRP1 knockdown in MCF10A mammary epithelial cells activates Wnt signaling and increases CD24 expression (a Wnt target gene); both SFRP1 and TCF-4 act as repressors of Wnt signaling in breast tissue. siRNA knockdown, CD24-luciferase reporter assay with TCF/LEF site mutagenesis, Western blot, flow cytometry for CD24 Oncogene Medium 16532032
2018 sFRP1 protects H9c2 cardiomyoblasts from doxorubicin-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway; in cardiomyocytes, intracellular sFRP1 interacts with PARP1 (identified by mass spectrometry co-IP); secreted sFRP1 has the opposite (cardiotoxic) effect by inhibiting canonical Wnt/β-catenin signaling. sFRP1 overexpression/knockdown in H9c2 cells, SP600125 (JNK inhibitor) treatment, mass spectrometry pull-down identifying PARP1 as binding partner, rat in vivo Dox model, Western blot for Wnt pathway components Acta pharmacologica Sinica / Archives of toxicology Medium 30377735 32238888
2019 HOTTIP lncRNA recruits DNMT3b to the SFRP1 promoter, inducing its methylation and silencing, thereby activating the Wnt signaling pathway in rheumatoid arthritis synovial fibroblasts; demonstrated by RNA pull-down, RIP, and ChIP assays. RNA pull-down, RIP, ChIP, methylation-specific PCR, bisulfite sequencing PCR, HOTTIP knockdown and SFRP1 overexpression in RASFs, rat RA model Molecular therapy. Nucleic acids Medium 31902746
2022 WAY-316606, a small molecule inhibitor of SFRP1, activates neural stem cells in the adult human subventricular zone both in vitro and in vivo under homeostatic conditions, suggesting SFRP1 promotes progenitor quiescence through Wnt pathway antagonism. Single-cell RNA-seq of human SVZ, in vitro neural stem cell activation assay, in vivo WAY-316606 administration in mouse brain Nature communications Medium 35210419
2013 AKT1 E17K mutation strongly upregulates SFRP1 expression in meningioma cells and HEK293 cells transfected with mutant AKT1E17K, but not wild-type AKT1, establishing SFRP1 as a downstream target of oncogenic AKT1E17K signaling. AKT1E17K transfection into HEK293 cells, immunohistochemistry for SFRP1 in 958 meningiomas, genotyping Acta neuropathologica Medium 24096618
2009 SFRP-1 and SFRP-2 are specifically expressed in osteoblasts in bone marrow; SFRP-1 (but not SFRP-2) reduces multipotent hematopoietic progenitor numbers and compromises long-term HSC repopulating activity in transplantation assays, differentiating their functional roles despite both inhibiting Wnt signaling in vitro. Immunostaining of bone marrow sections, in vitro CD34-KSL culture assays, long-term competitive repopulation transplantation assay in mice Biochemical and biophysical research communications Medium 19778523
2013 Promoter hypermethylation of DKK1 and SFRP1 in systemic sclerosis fibroblasts is mediated by DNA methyltransferases; inhibition with 5-aza-2'-deoxycytidine reactivates DKK1 and SFRP1 transcription, inhibits canonical Wnt signaling (Axin2 mRNA, β-catenin staining) in vitro and in vivo, and ameliorates experimental fibrosis in bleomycin-challenged mice. Methylation-specific PCR of patient fibroblasts and PBMCs, 5-aza treatment in vitro and in bleomycin mouse model, Axin2 mRNA and β-catenin readouts Annals of the rheumatic diseases Medium 23698475
2022 Loss of Sfrp1 depletes hair follicle stem cells (HFSCs) and accelerates the hair follicle cycle; restoration of HFSC pool in Sfrp1-/- mice is mediated through a BMP-AKT-GSK3β signaling cross-talk that downregulates β-catenin activity, a mechanism absent in Sfrp1+/- mice. Sfrp1-/- and Sfrp1+/- mouse models, flow cytometry for HFSC markers (Lgr5, Axin2), BMP receptor and GSK3β inhibitor treatment in keratinocytes, β-catenin activity assays Stem cells Medium 35689817
2020 Sfrp1 and Sfrp5 double knockout disturbs trophoblast differentiation in the ectoplacental cone by hyperactivating canonical Wnt-β-catenin signaling, which exhausts trophoblast precursors and causes overabundance of giant cells at the expense of spongiotrophoblast cells via repression of Ascl2 expression. Sfrp1/Sfrp5 double KO mice, trophoblast-specific β-catenin exon-3 deletion mouse model, trophoblast stem cell lines, Ascl2 expression analysis BMC biology Medium 33109217

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 The Wnt antagonist sFRP1 in colorectal tumorigenesis. Cancer research 238 14871816
2008 Increased expression of the WNT antagonist sFRP-1 in glaucoma elevates intraocular pressure. The Journal of clinical investigation 156 18274669
2013 The Wnt antagonists DKK1 and SFRP1 are downregulated by promoter hypermethylation in systemic sclerosis. Annals of the rheumatic diseases 151 23698475
2005 Identification of SFRP1 as a candidate mediator of stromal-to-epithelial signaling in prostate cancer. Cancer research 133 16288033
2004 Members of the Wnt, Fz, and Frp gene families expressed in postnatal mouse cerebral cortex. The Journal of comparative neurology 129 15116386
2006 Suppressing Wnt signaling by the hedgehog pathway through sFRP-1. The Journal of biological chemistry 128 17035233
2005 SFRP1 regulates the growth of retinal ganglion cell axons through the Fz2 receptor. Nature neuroscience 128 16172602
2006 Sfrp1 and Sfrp2 regulate anteroposterior axis elongation and somite segmentation during mouse embryogenesis. Development (Cambridge, England) 122 16467359
2007 Frequent loss of SFRP1 expression in multiple human solid tumours: association with aberrant promoter methylation in renal cell carcinoma. Oncogene 118 17353908
2006 Differential inhibition of Wnt-3a by Sfrp-1, Sfrp-2, and Sfrp-3. Developmental dynamics : an official publication of the American Association of Anatomists 107 16425220
2006 WNT antagonist, SFRP1, is Hedgehog signaling target. International journal of molecular medicine 100 16328026
2013 Hepatitis C virus core protein epigenetically silences SFRP1 and enhances HCC aggressiveness by inducing epithelial-mesenchymal transition. Oncogene 97 23770846
2017 Colorectal adenoma and cancer detection based on altered methylation pattern of SFRP1, SFRP2, SDC2, and PRIMA1 in plasma samples. Epigenetics 96 28753106
2020 Stromal SOX2 Upregulation Promotes Tumorigenesis through the Generation of a SFRP1/2-Expressing Cancer-Associated Fibroblast Population. Developmental cell 89 33207226
2006 Repressor roles for TCF-4 and Sfrp1 in Wnt signaling in breast cancer. Oncogene 89 16532032
2011 Expression and function of EZH2 in synovial fibroblasts: epigenetic repression of the Wnt inhibitor SFRP1 in rheumatoid arthritis. Annals of the rheumatic diseases 84 21515604
2013 AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry. Acta neuropathologica 83 24096618
2004 Methylation-associated silencing of the Wnt antagonist SFRP1 gene in human ovarian cancers. Cancer science 83 15471560
2013 Crystal structure of the FRP and identification of the active site for modulation of OCP-mediated photoprotection in cyanobacteria. Proceedings of the National Academy of Sciences of the United States of America 82 23716688
2020 Epigenetics of SFRP1: The Dual Roles in Human Cancers. Cancers 81 32074995
2013 MiR-328 promotes glioma cell invasion via SFRP1-dependent Wnt-signaling activation. Neuro-oncology 79 24305703
2007 SFRP1 suppressed hepatoma cells growth through Wnt canonical signaling pathway. International journal of cancer 78 17443492
2024 Sfrp1 inhibits lung fibroblast invasion during transition to injury-induced myofibroblasts. The European respiratory journal 76 38212077
2014 MiR-27a targets sFRP1 in hFOB cells to regulate proliferation, apoptosis and differentiation. PloS one 73 24625818
2012 Wnt antagonist SFRP1 functions as a secreted mediator of senescence. Molecular and cellular biology 70 22927647
2021 SFRP1 modulates astrocyte-to-microglia crosstalk in acute and chronic neuroinflammation. EMBO reports 58 34569685
2018 miR-1301-3p promotes prostate cancer stem cell expansion by targeting SFRP1 and GSK3β. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 58 29358129
2017 MiRNA-27a promotes the proliferation and invasion of human gastric cancer MGC803 cells by targeting SFRP1 via Wnt/β-catenin signaling pathway. American journal of cancer research 58 28401000
1994 Characterization of a rat C6 glioma-secreted follistatin-related protein (FRP). Cloning and sequence of the human homologue. European journal of biochemistry 58 7957230
2012 SFRP1 and SFRP2 dose-dependently regulate midbrain dopamine neuron development in vivo and in embryonic stem cells. Stem cells (Dayton, Ohio) 53 22290867
2017 In vivo and in vitro effects of microRNA-27a on proliferation, migration and invasion of breast cancer cells through targeting of SFRP1 gene via Wnt/β-catenin signaling pathway. Oncotarget 52 28099945
2018 miR-542-3p prevents ovariectomy-induced osteoporosis in rats via targeting SFRP1. Journal of cellular physiology 51 29319176
2000 Sfrp-1 and sfrp-2 are expressed in overlapping and distinct domains during chick development. Mechanisms of development 50 11025221
2017 MicroRNA-27a Promotes the Proliferation and Invasiveness of Colon Cancer Cells by Targeting SFRP1 through the Wnt/β-Catenin Signaling Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 49 28772260
2003 Secreted frizzled-related protein 1 (SFRP1) protects fibroblasts from ceramide-induced apoptosis. The Journal of biological chemistry 47 14581477
2014 Loss of Frzb and Sfrp1 differentially affects joint homeostasis in instability-induced osteoarthritis. Osteoarthritis and cartilage 45 25450854
2008 Inhibition of myoblast differentiation by Sfrp1 and Sfrp2. Cell and tissue research 42 18322704
2003 SFRP1 modulates retina cell differentiation through a beta-catenin-independent mechanism. Journal of cell science 42 12724355
2018 MiR-27a targets DKK2 and SFRP1 to promote reosseointegration in the regenerative treatment of peri-implantitis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 41 30151888
2017 MicroRNA-27a-3p Modulates the Wnt/β-Catenin Signaling Pathway to Promote Epithelial-Mesenchymal Transition in Oral Squamous Carcinoma Stem Cells by Targeting SFRP1. Scientific reports 41 28425477
2013 Mice deficient in Sfrp1 exhibit increased adiposity, dysregulated glucose metabolism, and enhanced macrophage infiltration. PloS one 39 24339864
2009 Down-regulation of sfrp1 in a mammary epithelial cell line promotes the development of a cd44high/cd24low population which is invasive and resistant to anoikis. Cancer cell international 39 19422694
2014 Secreted Frizzled-related protein 1 (Sfrp1) regulates the progression of renal fibrosis in a mouse model of obstructive nephropathy. The Journal of biological chemistry 38 25253698
2005 TSC-36/FRP inhibits vascular smooth muscle cell proliferation and migration. Experimental and molecular pathology 38 16256108
2014 Myofibroblast-derived SFRP1 as potential inhibitor of colorectal carcinoma field effect. PloS one 37 25405986
2012 Stromal factors SDF1α, sFRP1, and VEGFD induce dopaminergic neuron differentiation of human pluripotent stem cells. Journal of neuroscience research 37 22535492
2012 The Wnt inhibitor secreted Frizzled-Related Protein 1 (sFRP1) promotes human Th17 differentiation. European journal of immunology 37 22740051
2018 OCP-FRP protein complex topologies suggest a mechanism for controlling high light tolerance in cyanobacteria. Nature communications 36 30250028
2017 miR-1254 promotes lung cancer cell proliferation by targeting SFRP1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 35 28605875
2016 miR-1303 promotes the proliferation of neuroblastoma cell SH-SY5Y by targeting GSK3β and SFRP1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 35 27434867
2012 SFRP1 CpG island methylation locus is associated with renal cell cancer susceptibility and disease recurrence. Epigenetics 35 22419128
2010 Aberrant promoter methylation of WIF-1 and SFRP1, 2, 4 genes in mesothelioma. Oncology reports 35 20596629
2008 Methylation-associated silencing of SFRP1 in renal cell carcinoma. Oncology reports 34 18949430
2019 Aqueous humor levels of TGFβ2 and SFRP1 in different types of glaucoma. BMC ophthalmology 31 31382918
2012 Loss of SFRP1 promotes ductal branching in the murine mammary gland. BMC developmental biology 31 22928951
2019 miR‑144 promotes the proliferation and differentiation of bone mesenchymal stem cells by downregulating the expression of SFRP1. Molecular medicine reports 29 31115543
2022 Single-cell profiling of human subventricular zone progenitors identifies SFRP1 as a target to re-activate progenitors. Nature communications 28 35210419
2020 MicroRNA-27a targets Sfrp1 to induce renal fibrosis in diabetic nephropathy by activating Wnt/β-Catenin signalling. Bioscience reports 28 32484208
2019 Silencing of Long Non-coding RNA HOTTIP Reduces Inflammation in Rheumatoid Arthritis by Demethylation of SFRP1. Molecular therapy. Nucleic acids 28 31902746
2013 sFRP1 inhibits epithelial-mesenchymal transition in A549 human lung adenocarcinoma cell line. Cancer biotherapy & radiopharmaceuticals 28 23802127
2015 MiR-27a regulates Wnt/beta-catenin signaling through targeting SFRP1 in glioma. Neuroreport 27 26164457
2019 The Wnt Antagonist SFRP1: A Key Regulator of Periodontal Mineral Homeostasis. Stem cells and development 26 31215318
2018 Methylation of secreted frizzled-related protein 1 (SFRP1) promoter downregulates Wnt/β-catenin activity in keloids. Journal of molecular histology 26 29455276
2024 Fibroblast-derived extracellular vesicles contain SFRP1 and mediate pulmonary fibrosis. JCI insight 25 39315549
2020 LINC01089 Inhibits Tumorigenesis and Epithelial-Mesenchymal Transition of Non-small Cell Lung Cancer via the miR-27a/SFRP1/Wnt/β-catenin Axis. Frontiers in oncology 25 33282723
2015 DNA methylation level of OPCML and SFRP1: a potential diagnostic biomarker of cholangiocarcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 25 25652468
2009 Wnt modulators, SFRP-1, and SFRP-2 are expressed in osteoblasts and differentially regulate hematopoietic stem cells. Biochemical and biophysical research communications 25 19778523
2022 SFRP1 Negatively Modulates Pyroptosis of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis: A Review. Frontiers in immunology 24 35795672
2020 sFRP1 protects H9c2 cardiac myoblasts from doxorubicin-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway. Acta pharmacologica Sinica 24 32238888
2013 Tear levels of SFRP1 are significantly reduced in keratoconus patients. Molecular vision 24 23441124
2012 Reduced expression of Sfrp1 during chondrogenesis and in articular chondrocytes correlates with osteoarthritis in STR/ort mice. Experimental cell research 23 23261541
2011 Epigenetic inactivation of the SFRP1 gene in esophageal squamous cell carcinoma. Digestive diseases and sciences 23 21567192
2009 Differential methylation pattern of ID4, SFRP1, and SHP1 between acute myeloid leukemia and chronic myeloid leukemia. Journal of Korean medical science 23 19543515
2017 Dicer promotes tumorigenesis by translocating to nucleus to promote SFRP1 promoter methylation in cholangiocarcinoma cells. Cell death & disease 22 28230864
2010 Loss of SFRP1 expression is associated with aberrant beta-catenin distribution and tumor progression in mucoepidermoid carcinoma of salivary glands. Annals of surgical oncology 22 20162454
2019 Silencing microRNA-27a inhibits proliferation and invasion of human osteosarcoma cells through the SFRP1-dependent Wnt/β-catenin signaling pathway. Bioscience reports 21 31072914
2018 Methylation status of SFRP1, SFRP2, RASSF1A, RARβ and DAPK1 genes in patients with oral squamous cell carcinoma. Archives of oral biology 21 30576962
2006 The transcripts of SFRP1,CEP63 and EIF4G2 genes are frequently downregulated in transitional cell carcinomas of the bladder. Oncology 21 16410684
2020 SFRP1 in Skin Tumor Initiation and Cancer Stem Cell Regulation with Potential Implications in Epithelial Cancers. Stem cell reports 20 31928951
2001 Place- and time-dependent expression of mouse sFRP-1 during development of the cerebral neocortex. Mechanisms of development 20 11731256
2022 BMP-AKT-GSK3β Signaling Restores Hair Follicle Stem Cells Decrease Associated with Loss of Sfrp1. Stem cells (Dayton, Ohio) 19 35689817
2020 microRNA27a-3p mediates reduction of the Wnt antagonist sFRP-1 in systemic sclerosis. Epigenetics 19 32965161
2018 Sfrp1 attenuates TAC-induced cardiac dysfunction by inhibiting Wnt signaling pathway- mediated myocardial apoptosis in mice. Lipids in health and disease 18 30153824
2006 Role of secreted frizzled-related protein 1 (SFRP1) in wound healing. Journal of dental research 18 16567562
2002 Expression of Ngn1, Ngn2, Cash1, Gsh2 and Sfrp1 in the developing chick telencephalon. Mechanisms of development 18 11744393
2022 Nanoparticle-mediated selective Sfrp-1 silencing enhances bone density in osteoporotic mice. Journal of nanobiotechnology 17 36309688
2020 Hyperactivated Wnt-β-catenin signaling in the absence of sFRP1 and sFRP5 disrupts trophoblast differentiation through repression of Ascl2. BMC biology 17 33109217
2020 Oncogenic miR-27a delivered by exosomes binds to SFRP1 and promotes angiogenesis in renal clear cell carcinoma. Molecular therapy. Nucleic acids 17 33738141
2017 Methylation-associated silencing of SFRP1 gene in high-grade serous ovarian carcinomas. Annals of diagnostic pathology 17 29146058
2023 Exosomal microRNA‑4516, microRNA‑203 and SFRP1 are potential biomarkers of acute myocardial infarction. Molecular medicine reports 16 37203392
2022 Disruption of ZNF334 promotes triple-negative breast carcinoma malignancy through the SFRP1/ Wnt/β-catenin signaling axis. Cellular and molecular life sciences : CMLS 16 35507080
2022 Hsa_circ_0001445 works as a cancer suppressor via miR-576-5p/SFRP1 axis regulation in ovarian cancer. Cancer medicine 16 36259450
2018 sFRP1 has a biphasic effect on doxorubicin-induced cardiotoxicity in a cellular location-dependent manner in NRCMs and Rats. Archives of toxicology 16 30377735
2017 Effects of supplementation with nondigestible carbohydrates on fecal calprotectin and on epigenetic regulation of SFRP1 expression in the large-bowel mucosa of healthy individuals. The American journal of clinical nutrition 16 28077379
2012 SFRP1 promoter methylation and expression in human trabecular meshwork cells. Experimental eye research 16 22248913
2006 Aberrant methylation of secreted apoptosis-related protein 2 (SARP2) in pure pancreatic juice in diagnosis of pancreatic neoplasms. Pancreas 16 16670620
2021 A novel identified circ-ANKHD1 targets the miR-27a-3p/SFRP1 signaling pathway and modulates the apoptosis of granulosa cells. Environmental science and pollution research international 15 34091845
2014 Circulating SFRP1 promoter methylation status in gastric adenocarcinoma and esophageal square cell carcinoma. Biomedical reports 15 25469261
2005 Comparative genomics on SFRP1 orthologs. International journal of oncology 15 16077939
2004 Follistatin-related protein gene (FRP) is expressed in the synovial tissues of rheumatoid arthritis, but its polymorphisms are not associated with genetic susceptibility. Clinical and experimental rheumatology 15 15638044