Affinage

SFRP1

Secreted frizzled-related protein 1 · UniProt Q8N474

Length
314 aa
Mass
35.4 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SFRP1 is a secreted glycoprotein that modulates Wnt signaling and shapes cell fate, tissue morphogenesis, and stress responses across many contexts (PMID:16467359, PMID:22927647). It binds Wnt ligands physically (demonstrated by co-immunoprecipitation with Wnt-8) (PMID:10640709) and engages the Frizzled-2 receptor to redirect retinal ganglion cell axon growth through a Wnt-inhibition-independent, G-alpha-protein-dependent mechanism (PMID:16172602). Through canonical Wnt antagonism, SFRP1 reduces nuclear beta-catenin and suppresses growth and EMT in hepatoma and cervical cancer cells (PMID:17443492, PMID:19095296), and Sfrp1/Sfrp2 redundantly drive anteroposterior axis elongation, somite segmentation, and Notch oscillations during mouse embryogenesis (PMID:16467359). At low-to-medium concentrations SFRP1 instead activates the non-canonical Wnt/PCP–Rac1 pathway, phenocopying Wnt5a in dopaminergic neuron differentiation (PMID:22290867), and restrains JNK- and RHOA-driven fibroblast invasion and apoptosis independently of canonical beta-catenin signaling (PMID:25253698, PMID:38212077, PMID:32238888). SFRP1 also acts as a secreted mediator of stress-induced cellular senescence by inhibiting Wnt and activating the Rb pathway (PMID:22927647), potentiates TGF-beta/Smad signaling to drive Th17 differentiation (PMID:22740051), and amplifies astrocyte-to-microglia neuroinflammation via HIF-dependent pathways (PMID:34569685). SFRP1 expression is controlled both upstream — induced by Hedgehog/Gli1 to mediate Hedgehog–Wnt crosstalk (PMID:17035233) — and through epigenetic silencing by promoter DNA hypermethylation (via DNMT1/HDAC1) or H3K27me3 (via EZH2) (PMID:23770846, PMID:16410723, PMID:27570179, PMID:21515604). In contexts including gastric cancer and CAF-driven colorectal metastasis, SFRP1 exerts Wnt-independent tumor-promoting effects through GSK3beta/Rac1/Smad3 modulation or an FGFR2–HIF1 axis (PMID:30542739, PMID:40225580, PMID:25033833), and fibroblast-derived extracellular vesicles deliver SFRP1 to activate WNT/beta-catenin in alveolar cells during pulmonary fibrosis (PMID:39315549).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2000 Medium

    Establishing whether SFRP1 physically engages Wnt ligands was the foundational question for assigning it a Wnt-modulatory role.

    Evidence co-immunoprecipitation of the bovine sFRP-1 counterpart (FrzA) with mWnt-8 in cell culture, with overlapping cardiac expression

    PMID:10640709

    Open questions at the time
    • Direct binding shown for a bovine homolog only
    • Functional consequence of the interaction not tested
    • No affinity or stoichiometry measured
  2. 2005 High

    Whether SFRP1 signals through a receptor independently of Wnt antagonism was resolved by showing it acts via Frizzled-2 to guide axons.

    Evidence Fz2 loss-of-function and growth-cone assays in chick and Xenopus retinal ganglion cells with G-alpha and protein-synthesis pharmacology

    PMID:16172602

    Open questions at the time
    • Direct SFRP1–Fz2 binding not biochemically resolved
    • Intracellular transduction from Fz2 to cytoskeleton incompletely defined
  3. 2006 High

    How SFRP1 is positioned in pathway crosstalk was addressed by identifying Hedgehog/Gli1 as a direct transcriptional inducer linking Hedgehog to Wnt suppression.

    Evidence ChIP showing Gli1 promoter binding plus Gli1 gain-of-function and SFRP1 knockdown with beta-catenin readouts

    PMID:17035233

    Open questions at the time
    • Generality across non-gastric tissues not established
    • Quantitative contribution of SFRP1 to Hedgehog–Wnt crosstalk unclear
  4. 2006 High

    The developmental necessity of SFRP1 as a Wnt antagonist was demonstrated through redundancy with SFRP2 in axial patterning.

    Evidence Sfrp1/Sfrp2 compound knockout mice with somite and Lfng/Hes7 in situ readouts

    PMID:16467359

    Open questions at the time
    • Molecular link between SFRP loss and Notch oscillation disruption not defined
    • Single knockouts uninformative due to redundancy
  5. 2007 Medium

    Whether SFRP1 re-expression can reverse oncogenic Wnt activation was tested, showing beta-catenin-dependent growth suppression in hepatoma.

    Evidence SFRP1 re-expression and RNAi across hepatoma lines with differing beta-catenin status, Wnt reporter and proliferation assays

    PMID:17443492

    Open questions at the time
    • No effect in truncated-beta-catenin cells indicates context dependence
    • In vivo tumor relevance not tested here
  6. 2008 High

    SFRP1's role in tissue physiology beyond development was extended to intraocular pressure regulation via Wnt/beta-catenin in the trabecular meshwork.

    Evidence ex vivo human eye perfusion with recombinant SFRP1, adenoviral overexpression in mice, and pharmacological Wnt rescue

    PMID:18274669

    Open questions at the time
    • Receptor mediating the trabecular meshwork effect not identified
    • Link to human glaucoma genetics not established here
  7. 2008 Medium

    The anti-tumor/anti-EMT capacity of SFRP1 was generalized to cervical cancer via beta-catenin and EMT-factor suppression.

    Evidence SFRP1/SFRP2 overexpression and shRNA with E-cadherin, SLUG/TWIST/SNAIL readouts and xenografts

    PMID:19095296

    Open questions at the time
    • Direct receptor engagement not addressed
    • Single lab
  8. 2009 Medium

    Whether SFRP1 distinctively regulates stem cell pools was probed, showing it (not SFRP2) suppresses HSC repopulating activity.

    Evidence in vitro HSC culture with SFRP1/SFRP2 and in vivo long-term transplantation assays

    PMID:19778523

    Open questions at the time
    • Signaling pathway behind HSC suppression not defined
    • Mechanism distinguishing SFRP1 from SFRP2 unknown
  9. 2010 Medium

    The requirement for SFRP1 in organ morphogenesis was extended to lung alveologenesis, alongside an MMP-inducing activity in adult epithelium.

    Evidence Sfrp1-/- mouse lung morphology plus SFRP1 overexpression in human lung epithelial cells with ERK/MMP readouts

    PMID:20595636

    Open questions at the time
    • Two functional contexts in one study not mechanistically unified
    • How SFRP1 activates ERK/MMP not resolved
  10. 2012 High

    SFRP1 was defined as a secreted effector of cellular senescence acting through Wnt inhibition and Rb activation.

    Evidence knockdown/overexpression and cancer-mutant constructs with SA-beta-gal, BrdU, and Rb pathway readouts

    PMID:22927647

    Open questions at the time
    • Receptor coupling senescence signal not mapped
    • How cancer mutants lose function structurally unclear
  11. 2012 High

    The concentration-dependent switch to non-canonical Wnt/PCP–Rac1 signaling was established in dopaminergic neuron specification.

    Evidence Sfrp1/Sfrp2 compound knockout phenocopying Wnt5a-/- plus dose-response progenitor cultures

    PMID:22290867

    Open questions at the time
    • Molecular basis of the concentration-dependent canonical/non-canonical switch unknown
    • Receptor selectivity not defined
  12. 2012 Medium

    SFRP1's developmental restraint on Wnt-driven proliferation was shown in the mammary gland.

    Evidence Sfrp1-/- whole mounts, Axin2 reporter explants, mammosphere and gene-expression analysis

    PMID:22928951

    Open questions at the time
    • Causal driver among altered Wnt targets not isolated
    • Tumor relevance not directly tested
  13. 2013 Medium

    An immunological function was added by showing SFRP1 potentiates TGF-beta/Smad signaling to drive Th17 differentiation.

    Evidence recombinant sFRP1 on human CD4+ T cells with IL-17, phospho-Smad2/3, and TGF-beta blockade

    PMID:22740051

    Open questions at the time
    • How SFRP1 potentiates TGF-beta receptor signaling mechanistically unknown
    • Single cell type
  14. 2013 High

    The mechanism of SFRP1 silencing in virally driven cancer was defined as DNMT1/HDAC1-mediated promoter hypermethylation with functional consequences.

    Evidence ChIP for DNMT1/HDAC1 promoter occupancy, DNMT1 knockdown, SFRP1 restoration, and xenografts with EMT/Wnt readouts

    PMID:23770846

    Open questions at the time
    • Whether this silencing route operates outside HCV-core context unclear
  15. 2014 High

    SFRP1 was shown to restrain fibrotic fibroblast behavior through the non-canonical RHOA/PCP pathway rather than canonical Wnt.

    Evidence human lung fibroblast loss-of-function with invasion and RHOA assays, and Sfrp1 KO renal obstruction model with JNK/EMT readouts

    PMID:25253698 PMID:38212077

    Open questions at the time
    • Receptor mediating RHOA/JNK modulation not identified
    • Cross-tissue generality of the anti-fibrotic role partly inferred
  16. 2016 Medium

    Distinct epigenetic silencing routes were resolved, showing SFRP1 can be repressed by H3K27me3 or DNA hypermethylation depending on cell context.

    Evidence ChIP for H3K27me3, bisulfite sequencing across prostate cell lines; EZH2 gain/loss in RA synovial fibroblasts; cooperative methylation/acetylation in esophageal and breast cancer cells

    PMID:16410723 PMID:21515604 PMID:21567192 PMID:27570179 PMID:30000000

    Open questions at the time
    • Determinants selecting one silencing mode over another unknown
    • Mostly single-lab, cell-line-based studies
  17. 2016 Medium

    Wnt-independent functions of SFRP1 were established in triple-negative breast cancer affecting chemoresistance and migration.

    Evidence siRNA knockdown in TNBC lines with chemo-sensitivity, apoptosis, migration assays and negative Wnt reporter result

    PMID:25033833

    Open questions at the time
    • The Wnt-independent effector pathways not molecularly defined
    • Single lab
  18. 2021 Medium

    A neuroinflammatory amplifier role was defined whereby astrocyte-derived SFRP1 sustains microglial activation via HIF-dependent signaling.

    Evidence mouse acute/chronic neuroinflammation models and astrocyte/microglia co-cultures with HIF and NF-kappaB readouts

    PMID:34569685

    Open questions at the time
    • Microglial receptor for SFRP1 not identified
    • Relative contribution of HIF vs NF-kappaB unresolved
  19. 2024 High

    SFRP1 was shown to be delivered via fibroblast extracellular vesicles to drive alveolar Wnt/beta-catenin activation and pulmonary fibrosis.

    Evidence proteomics of BALF-EVs, Sfrp1 KO in vivo fibrosis assay, precision-cut lung slices, and primary AT2 cell treatment with keratin 8/Wnt readouts

    PMID:39315549

    Open questions at the time
    • How SFRP1 packaged into EVs is regulated unknown
    • Receptor on AT2 cells mediating Wnt activation not identified
  20. 2025 Medium

    A pro-metastatic stromal axis was defined whereby CAF-derived SFRP1 acts through FGFR2/HIF1 to enhance tumor stemness and metastasis.

    Evidence recombinant SFRP1 and CAF conditioned medium, orthotopic metastasis models, scRNA-seq and spatial transcriptomics

    PMID:40225580

    Open questions at the time
    • SFRP1–FGFR2 interaction inferred from signaling, not direct binding
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved which receptor(s) and structural determinants dictate SFRP1's switch between Wnt-antagonist, non-canonical PCP, TGF-beta-potentiating, and Wnt-independent (FGFR2/GSK3beta-Rac1) signaling across tissues.
  • No unifying structure-function map of SFRP1 receptor selectivity
  • Concentration-dependent canonical/non-canonical switch mechanism undefined
  • Direct binding partners beyond Fz2 and Wnt-8 not biochemically confirmed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0048018 receptor ligand activity 3
Localization
GO:0005576 extracellular region 4 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
FGFR2FZD2WNT8

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 SFRP1 directly interacts with Frizzled-2 (Fz2) receptor and this interaction is required for SFRP1-mediated reorientation of retinal ganglion cell axon growth; interference with Fz2 expression abolishes growth cone responses to SFRP1. This axon guidance activity does not require Wnt inhibition and is modulated by extracellular matrix molecules; intracellularly, it requires G-alpha protein activation, protein synthesis and degradation, and is modulated by cyclic nucleotide levels. Fz2 loss-of-function (interference experiments), growth cone response assays in chick and Xenopus retinal ganglion cells, pharmacological inhibition of G-alpha proteins and protein synthesis/degradation Nature neuroscience High 16172602
2006 SFRP1 expression in mouse embryonic fibroblasts and human gastric cancer cells is transcriptionally regulated by Gli1 (and Gli2), downstream transcription factors of the Hedgehog signaling pathway; chromatin immunoprecipitation demonstrated direct Gli1 binding to the SFRP1 promoter. SFRP1 induction by Hedgehog/Gli1 suppresses Wnt-1-mediated beta-catenin accumulation and DKK1 expression, establishing SFRP1 as a mediator of Hedgehog-Wnt pathway cross-talk. Chromatin immunoprecipitation, ectopic Gli1 expression, siRNA knockdown of SFRP1, beta-catenin accumulation assay, smoothened antagonist (KAAD-cyclopamine) treatment The Journal of biological chemistry High 17035233
2006 Sfrp1 and Sfrp2 are functionally redundant secreted Wnt antagonists required for anteroposterior axis elongation and somite segmentation in mouse embryogenesis; compound Sfrp1/Sfrp2 double-knockout mice show severe thoracic shortening, aberrant pre-somitic mesoderm cell migration, and disrupted Notch signaling oscillations (abnormal Lfng and Hes7 expression), while single knockouts have no detectable phenotype. Double homozygous mouse knockout, in situ hybridization for Lfng and Hes7, histological analysis of somite segmentation Development (Cambridge, England) High 16467359
2008 Recombinant SFRP1 protein added to ex vivo perfusion-cultured human eyes decreases aqueous humor outflow facility concomitant with reduced beta-catenin levels in the trabecular meshwork; adenoviral overexpression of SFRP1 in mouse eyes produced a titer-dependent, approximately 2-fold increase in intraocular pressure that was reduced by topical administration of a downstream Wnt signaling inhibitor. SFRP1 is overexpressed in glaucomatous trabecular meshwork cells. Ex vivo human eye perfusion culture with recombinant SFRP1, adenoviral intravitreal injection in mice, pharmacological inhibition of downstream Wnt signaling, beta-catenin measurement The Journal of clinical investigation High 18274669
2012 SFRP1 is oversecreted upon DNA damage- or oxidative stress-induced cellular senescence and is necessary for stress-induced senescence (knockdown prevents senescence) and sufficient to induce senescence phenotypes. SFRP1 functions as a secreted mediator of senescence through inhibition of Wnt signaling and activation of the retinoblastoma (Rb) pathway; cancer-associated SFRP1 mutants are defective for senescence induction. Knockdown/overexpression of SFRP1, secreted protein quantification, senescence assays (SA-beta-gal, BrdU), Rb pathway activation measurement, cancer-mutant constructs Molecular and cellular biology High 22927647
2012 SFRP1 and SFRP2 activate the Wnt/planar-cell-polarity (PCP)/Rac1 pathway in dopamine cells; compound Sfrp1-/-;Sfrp2-/- mice display a Wnt/PCP phenotype (anteroposterior shortening of ventral midbrain, lateral expansion of Shh domain and DA lineage markers, accumulation of Nurr1+ precursors) similar to Wnt5a-/- mice. Low-to-medium concentrations of sFRP1 promote dopaminergic differentiation of progenitors in vitro, mimicking Wnt5a. Compound knockout mouse model, immunofluorescence, in vitro primary ventral midbrain culture and embryonic stem cell differentiation with sFRP1/sFRP2 treatment Stem cells (Dayton, Ohio) High 22290867
2010 SFRP1 knockout mice exhibit aberrant Wnt signaling, mesenchymal proliferation, and impaired alveolar formation during lung development, demonstrating SFRP1 is essential for normal alveologenesis. Conversely, SFRP1 expression in adult human lung epithelial cells activates ERK and upregulates MMP1 and MMP9 without altering TIMP1 production. Sfrp1-/- mouse model (morphological analysis, Wnt signaling readouts), overexpression of SFRP1 in human lung epithelial cells with ERK activation and MMP/TIMP measurement The American journal of pathology Medium 20595636
2003 SFRP1 protects fibroblasts from ceramide-induced apoptosis; inhibition of endogenous SFRP1 increased cell death in periodontal ligament fibroblasts, while exogenous SFRP1 reduced apoptosis in gingival fibroblasts. This anti-apoptotic effect is linked to regulation of p53, caspase-3, caspase-9, and BIK expression. In vivo, exogenous SFRP1 reduced apoptosis in dermal fibroblasts. Antisense inhibition of endogenous SFRP1, exogenous SFRP1 protein addition, apoptosis assays, in vivo dermal fibroblast model, western blot/RT-PCR for apoptosis genes The Journal of biological chemistry Medium 14581477
2007 Restoration of SFRP1 expression in beta-catenin-mutant hepatoma cells (Huh6) attenuated Wnt/beta-catenin signaling, decreased nuclear beta-catenin accumulation, and suppressed cell growth; knockdown of SFRP1 by RNAi in beta-catenin-deficient SK-Hep1 cells stimulated Wnt signaling and promoted cell growth. SFRP1 restoration had no effect in HepG2 cells with truncated beta-catenin, indicating beta-catenin-dependent suppression. SFRP1 re-expression in hepatoma cell lines, RNAi knockdown, nuclear beta-catenin immunofluorescence, Wnt reporter assay, proliferation assay International journal of cancer Medium 17443492
2011 EZH2 (histone methyltransferase) is overexpressed in rheumatoid arthritis synovial fibroblasts (RASF), further induced by TNF-alpha via NF-kappaB and JNK pathways, and mediates epigenetic repression of SFRP1; chromatin immunoprecipitation showed altered activating and silencing histone marks at the SFRP1 promoter correlated with EZH2 occupancy. ChIP for histone marks at SFRP1 promoter, EZH2 overexpression/siRNA knockdown, reporter gene assays, kinase inhibitor experiments Annals of the rheumatic diseases Medium 21515604
2013 HCV core protein downregulates SFRP1 by inducing hypermethylation of CpG islands in the SFRP1 promoter; ChIP revealed that HCV core protein increased binding of DNMT1 and HDAC1 to the SFRP1 promoter TSS with concomitant reduction of acetyl-histone H3 binding. Dnmt1 knockdown or SFRP1 restoration abolished core protein-induced cell proliferation, migration, invasiveness, EMT, and beta-catenin/Wnt target gene activation in vitro and in xenograft models. Chromatin immunoprecipitation, DNA methylation analysis, DNMT1 knockdown, SFRP1 overexpression, xenograft tumor model, western blot for EMT and Wnt pathway markers Oncogene High 23770846
2008 Restoration of SFRP1 or SFRP2 expression in cervical cancer cells attenuated Wnt signaling, decreased nuclear beta-catenin accumulation, suppressed cell growth, enhanced E-cadherin expression, and inhibited expression of EMT transcription factors SLUG, TWIST, and SNAIL. In xenograft models, SFRP1 suppressed tumor growth in vivo. SFRP1/SFRP2 overexpression and shRNA knockdown in cervical cancer cells, nuclear beta-catenin localization, E-cadherin and EMT marker western blot/RT-PCR, xenograft tumor model Gynecologic oncology Medium 19095296
2014 TGF-beta1 downregulates SFRP1 in noninvasive transitional lung fibroblasts and induces their switch to an invasive CTHRC1+ myofibroblast identity; SFRP1 loss-of-function (in human lung fibroblasts) modulates TGF-beta1-induced fibroblast invasion and RHOA pathway activity. Loss-of-function studies in patient-derived human lung fibroblasts, cell invasion assays, RHOA pathway activity measurement, spatial transcriptomics, multiplexed immunostaining, single-cell RNA sequencing The European respiratory journal High 38212077
2014 Sfrp1 deficiency in a mouse model of unilateral ureteral obstruction increases expression of myofibroblast markers (alpha-SMA), vimentin, and decreases E-cadherin (enhanced EMT), with elevated phospho-c-Jun and JNK and increased apoptosis, but no change in canonical Wnt signaling; establishing that Sfrp1 restrains renal fibrosis through the non-canonical Wnt/PCP pathway rather than the canonical beta-catenin pathway. Sfrp1 knockout mouse, unilateral ureteral obstruction model, immunoblotting for alpha-SMA/vimentin/E-cadherin/p-c-Jun/JNK/beta-catenin, apoptosis assay The Journal of biological chemistry High 25253698
2012 Loss of SFRP1 in mice leads to hyperplastic mammary gland ductal branching with lobulo-alveolar development in virgin glands normally not present until pregnancy; SFRP1-/- glands show elevated Axin2 (Wnt target), altered c-Myc, TGFbeta-2, Wnt4, RANKL, and Rspo2 expression, and increased mammary epithelial cell mammosphere formation capacity. Sfrp1-/- mouse model, mammary gland whole mounts/histomorphometry, explant cultures with Axin2 reporter, mammosphere assay, gene expression analysis BMC developmental biology Medium 22928951
2013 SFRP1 promotes Th17 cell differentiation in human CD4+ T cells; sFRP1 significantly enhanced phosphorylation of Smad2/3 in CD4+ T cells upon TGF-beta stimulation, and blocking TGF-beta signaling abolished sFRP1's Th17-promoting activity, indicating sFRP1 potentiates TGF-beta/Smad signaling to drive Th17 differentiation. Addition of recombinant sFRP1 to human CD4+ T cell cultures under Th17 differentiation conditions, IL-17 cytokine measurement, phospho-Smad2/3 immunoblotting, TGF-beta signaling blockade European journal of immunology Medium 22740051
2021 SFRP1 (largely astrocyte-derived) promotes and sustains microglial activation in mouse models of acute and chronic neuroinflammation; SFRP1 upregulates components of the HIF-dependent inflammatory pathway and, to a lesser extent, NF-kappaB pathway components, establishing SFRP1 as an astrocyte-to-microglia amplifier of neuroinflammation. Mouse neuroinflammation models (acute and chronic), astrocyte/microglia co-culture experiments, pathway analysis of HIF and NF-kappaB targets EMBO reports Medium 34569685
2022 SFRP1 maintains the quiescent state of human subventricular zone progenitors; administration of WAY-316606 (small-molecule SFRP1 inhibitor) stimulates neural stem cell activation both in vitro and in vivo under homeostatic conditions. SFRP1 inhibition using WAY-316606 in vitro (human SVZ progenitor cultures) and in vivo, single-cell RNA sequencing of CD271+ progenitors Nature communications Medium 35210419
2024 Fibroblast-derived extracellular vesicles are enriched in SFRP1; vesicular SFRP1 promotes lung fibrosis, leads to increased transitional cell markers (keratin 8) and WNT/beta-catenin signaling in primary alveolar type 2 cells, and Sfrp1 deficiency inhibits the pro-fibrotic activity of fibroblast-derived EVs in vivo. Label-free proteomics of BALF-EVs from bleomycin-challenged mice, Sfrp1 KO mouse in vivo fibrosis assay, precision-cut lung slice ex vivo model, primary alveolar type 2 cell treatment with SFRP1, WNT/beta-catenin and keratin 8 readouts JCI insight High 39315549
2019 SFRP1 overexpression in gastric cancer cells restores GSK3beta activity, which activates Rac1; GSK3beta and Rac1 mediate SFRP1-induced increase in cell growth and migration/invasion, and restrain TGF-beta/Smad3 signaling by preventing Smad3 nuclear translocation. Inhibition of GSK3beta or Rac1 abolished SFRP1's effects on the aggressive phenotype. SFRP1 overexpression and knockdown, GSK3beta/Rac1 inhibition, immunoblotting, confocal immunofluorescence for Smad3 subcellular localization, migration/invasion assays Oncology reports Medium 30542739
2020 sFRP1 protects H9c2 cardiac myoblasts from doxorubicin-induced apoptosis by inhibiting the Wnt/PCP-JNK (non-canonical) pathway; overexpression of sFRP1 reduced Wnt/PCP-JNK signaling and apoptosis, while SP600125 (JNK inhibitor) mimicked this protection; in a rat cardiotoxicity model, doxorubicin suppressed sFRP1 with concomitant Wnt/PCP-JNK activation. sFRP1 overexpression in H9c2 cells, JNK inhibitor treatment, doxorubicin rat model, apoptosis assays, western blot for Wnt/PCP-JNK pathway components Acta pharmacologica Sinica Medium 32238888
2014 miR-1260b directly targets and represses SFRP1 (and Smad4) as confirmed by 3'UTR luciferase assay; genistein downregulates miR-1260b and upregulates SFRP1 and Smad4 expression via DNA demethylation and histone modifications in prostate cancer cells. 3'UTR luciferase assay, western blot, genistein treatment, miR-1260b knockdown, proliferation/invasion/migration assays, TCF reporter activity British journal of cancer Medium 24504368
2013 miR-328 directly targets SFRP1 (confirmed by 3'UTR luciferase assay) and reduces SFRP1 protein levels, activating Wnt signaling; miR-328 is upregulated in invading glioma cells in vivo and promotes glioma cell invasion. 3'UTR luciferase assay, miRNA mimics/inhibitors, TCF/LEF reporter assay, invasion assays Neuro-oncology Medium 24305703
2019 SFRP1 inhibition in periodontal ligament (PDL) progenitors using WAY-316606 or RNA silencing increases PDL cell mineralization and upregulates mineralization genes (beta-catenin, alkaline phosphatase, osteocalcin, collagen I, RUNX2); SFRP1 knockdown promotes PDL differentiation through histone H3K4me3-mediated activation of RUNX2 and SP7. The same interventions had little effect on alveolar bone progenitors, except for osteocalcin upregulation. Small molecule SFRP1 inhibition (WAY-316606), RNA silencing, ChIP for H3K4me3 at RUNX2 and SP7 promoters, mineralization assays, western blot, comparative analysis in PDL vs. alveolar bone progenitors Stem cells and development Medium 31215318
2000 The bovine counterpart of murine sFRP-1 (FrzA) binds mWnt-8 in cell culture immunoprecipitation experiments; sFRP-1 and mWnt-8 display overlapping expression patterns in cardiomyocytes during mouse heart morphogenesis. Co-immunoprecipitation of FrzA (sFRP-1 bovine counterpart) and mWnt-8 in cell culture, in situ expression pattern analysis Mechanisms of development Medium 10640709
2013 AKT1 E17K mutation in meningiomas strongly upregulates SFRP1 expression; HEK293 cells transfected with mutant AKT1E17K (but not wild-type) also show SFRP1 upregulation, indicating that activated AKT1 signaling positively regulates SFRP1 expression. Transfection of HEK293 cells with mutant vs. wild-type AKT1E17K, SFRP1 immunohistochemistry in tumor samples, mutation analysis of 1,437 tumors Acta neuropathologica Medium 24096618
2016 SFRP1 expression in triple-negative breast cancer cells does not affect Wnt signaling upon knockdown; instead, SFRP1 knockdown renders cells more resistant to chemotherapy, reduces apoptosis, and modifies migration/invasion capacity through Wnt-independent pathways, with differential regulation of pro-apoptotic and migratory pathways. siRNA-mediated SFRP1 knockdown in TNBC cell lines, chemotherapy sensitivity assays, apoptosis assays, migration/invasion assays, Wnt pathway reporter assays (negative result for Wnt) Molecular cancer Medium 25033833
2009 SFRP1 (but not SFRP2) expressed by osteoblasts in bone marrow reduces the number of multipotent hematopoietic progenitors in vitro and compromises the long-term repopulating activity of hematopoietic stem cells in transplantation assays; SFRP2 did not affect or even enhanced HSC repopulating activity under the same conditions. In vitro culture of CD34-KSL HSCs with SFRP1 or SFRP2, in vivo HSC transplantation assay for long-term repopulation, immunostaining of bone marrow Biochemical and biophysical research communications Medium 19778523
2014 Loss of Sfrp1 (but not Frzb) in the DMM mouse model of osteoarthritis significantly alters subchondral bone properties without affecting cartilage OA severity scores, whereas Frzb loss increases tibial OA severity; establishing that SFRP1 and FRZB differentially modulate Wnt signaling in distinct joint compartments. Sfrp1-/- and Frzb-/- mice in destabilization of medial meniscus (DMM) model, OARSI histopathology scoring, histomorphometry of subchondral bone Osteoarthritis and cartilage Medium 25450854
2006 SFRP1 promoter hypermethylation in breast cancer cell lines is the predominant epigenetic mechanism for gene silencing; treatment with 5-azaC (demethylating agent) restores SFRP1 mRNA expression; histone deacetylation may act in conjunction. Methylation-specific PCR, bisulfite sequencing, 5-azaC treatment, quantitative RT-PCR Cancer biology & therapy Medium 16410723
2011 In esophageal squamous cell carcinoma, combined treatment with 5-aza-2'-deoxycytidine (DAC) and trichostatin A (TSA) is required to rescue SFRP1 mRNA expression; individual treatment with either agent was insufficient; ChIP demonstrated that acetylated H3 and H4 are present at the SFRP1 promoter, indicating cooperative DNA methylation and histone acetylation regulation of SFRP1 expression. 5-aza-dC and TSA treatments (individual and combined), ChIP for acetylated H3/H4 at SFRP1 promoter, RT-PCR for SFRP1 mRNA Digestive diseases and sciences Medium 21567192
2016 In LNCaP prostate cancer cells, SFRP1 repression occurs not through DNA methylation but through an aberrant gain of the repressive histone mark H3K27me3 at the SFRP1 promoter; in PC3 cells, DNA hypermethylation is the operative mechanism. This establishes that SFRP1 can be silenced by two distinct epigenetic mechanisms. Methylation-specific PCR, bisulfite sequencing, ChIP for H3K27me3 at SFRP1 promoter, qRT-PCR in prostatic cell lines and tissues Gene Medium 27570179
2025 In colorectal cancer, FOS-driven inflammatory CAF-derived SFRP1 binds to FGFR2 on tumor cells, activating HIF1 signaling to enhance tumor stemness, EMT, and liver metastasis; in vitro and in vivo experiments with recombinant SFRP1, conditioned medium from SFRP1-overexpressing CAFs, and orthotopic metastasis models confirmed this SFRP1-FGFR2-HIF1 axis. Recombinant SFRP1 treatment of cancer cells, conditioned medium from CAF-Sfrp1 cells, xenograft and orthotopic mouse models, single-cell RNA sequencing, spatial transcriptomics, pathway analysis Theranostics Medium 40225580

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 239 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 152 23698475
2006 Suppressing Wnt signaling by the hedgehog pathway through sFRP-1. The Journal of biological chemistry 129 17035233
2005 SFRP1 regulates the growth of retinal ganglion cell axons through the Fz2 receptor. Nature neuroscience 129 16172602
2004 Deletions of chromosome 8p and loss of sFRP1 expression are progression markers of papillary bladder cancer. Laboratory investigation; a journal of technical methods and pathology 127 14968126
2008 SFRP1 and SFRP2 suppress the transformation and invasion abilities of cervical cancer cells through Wnt signal pathway. Gynecologic oncology 122 19095296
2006 Sfrp1 and Sfrp2 regulate anteroposterior axis elongation and somite segmentation during mouse embryogenesis. Development (Cambridge, England) 122 16467359
2014 Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells. British journal of cancer 111 24504368
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 98 23770846
2017 Colorectal adenoma and cancer detection based on altered methylation pattern of SFRP1, SFRP2, SDC2, and PRIMA1 in plasma samples. Epigenetics 96 28753106
1995 Molecular characterization of fusion regulatory protein-1 (FRP-1) that induces multinucleated giant cell formation of monocytes and HIV gp160-mediated cell fusion. FRP-1 and 4F2/CD98 are identical molecules. Journal of immunology (Baltimore, Md. : 1950) 93 7561057
2024 Sfrp1 inhibits lung fibroblast invasion during transition to injury-induced myofibroblasts. The European respiratory journal 86 38212077
2020 Epigenetics of SFRP1: The Dual Roles in Human Cancers. Cancers 85 32074995
2011 Expression and function of EZH2 in synovial fibroblasts: epigenetic repression of the Wnt inhibitor SFRP1 in rheumatoid arthritis. Annals of the rheumatic diseases 85 21515604
2013 AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry. Acta neuropathologica 84 24096618
2004 Methylation-associated silencing of the Wnt antagonist SFRP1 gene in human ovarian cancers. Cancer science 84 15471560
2006 Promoter methylation of the secreted frizzled-related protein 1 gene SFRP1 is frequent in hepatocellular carcinoma. Cancer 83 16795071
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
1998 Expression pattern of two Frizzled-related genes, Frzb-1 and Sfrp-1, during mouse embryogenesis suggests a role for modulating action of Wnt family members. Developmental dynamics : an official publication of the American Association of Anatomists 78 9671940
2006 Epigenetic suppression of secreted frizzled related protein 1 (SFRP1) expression in human breast cancer. Cancer biology & therapy 76 16410723
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 61 34569685
2018 miR-1301-3p promotes prostate cancer stem cell expansion by targeting SFRP1 and GSK3β. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 59 29358129
2014 Influence of secreted frizzled receptor protein 1 (SFRP1) on neoadjuvant chemotherapy in triple negative breast cancer does not rely on WNT signaling. Molecular cancer 55 25033833
2012 SFRP1 and SFRP2 dose-dependently regulate midbrain dopamine neuron development in vivo and in embryonic stem cells. Stem cells (Dayton, Ohio) 53 22290867
2018 miR-542-3p prevents ovariectomy-induced osteoporosis in rats via targeting SFRP1. Journal of cellular physiology 51 29319176
2015 DNA hypermethylation and decreased mRNA expression of MAL, PRIMA1, PTGDR and SFRP1 in colorectal adenoma and cancer. BMC cancer 51 26482433
2015 Wnt pathway antagonists, SFRP1, SFRP2, SOX17, and PPP2R2B, are methylated in gliomas and SFRP1 methylation predicts shorter survival. Journal of applied genetics 50 26337424
2000 Sfrp-1 and sfrp-2 are expressed in overlapping and distinct domains during chick development. Mechanisms of development 50 11025221
2010 The divergent roles of secreted frizzled related protein-1 (SFRP1) in lung morphogenesis and emphysema. The American journal of pathology 48 20595636
2016 Over-expression of microRNA-940 promotes cell proliferation by targeting GSK3β and sFRP1 in human pancreatic carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 47 27459115
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 46 25450854
2010 The advantages and disadvantages of sfrp1 and sfrp2 expression in pathological events. The Tohoku journal of experimental medicine 43 20448436
2000 Expression pattern of mouse sFRP-1 and mWnt-8 gene during heart morphogenesis. Mechanisms of development 43 10640709
2019 Exosomal miR-196a-1 promotes gastric cancer cell invasion and metastasis by targeting SFRP1. Nanomedicine (London, England) 39 31609675
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
2014 Myofibroblast-derived SFRP1 as potential inhibitor of colorectal carcinoma field effect. PloS one 38 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
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
2012 Loss of SFRP1 promotes ductal branching in the murine mammary gland. BMC developmental biology 32 22928951
1997 Paramyxovirus-induced syncytium cell formation is suppressed by a dominant negative fusion regulatory protein-1 (FRP-1)/CD98 mutated construct: an important role of FRP-1 in virus-induced cell fusion. The Journal of general virology 32 9129649
2019 Aqueous humor levels of TGFβ2 and SFRP1 in different types of glaucoma. BMC ophthalmology 31 31382918
2016 SFRP1 repression in prostate cancer is triggered by two different epigenetic mechanisms. Gene 31 27570179
2020 MicroRNA-27a targets Sfrp1 to induce renal fibrosis in diabetic nephropathy by activating Wnt/β-Catenin signalling. Bioscience reports 30 32484208
2022 Single-cell profiling of human subventricular zone progenitors identifies SFRP1 as a target to re-activate progenitors. Nature communications 29 35210419
2019 miR‑144 promotes the proliferation and differentiation of bone mesenchymal stem cells by downregulating the expression of SFRP1. Molecular medicine reports 29 31115543
2024 Fibroblast-derived extracellular vesicles contain SFRP1 and mediate pulmonary fibrosis. JCI insight 28 39315549
2017 MiR-1-3p Suppresses the Proliferation, Invasion and Migration of Bladder Cancer Cells by Up-Regulating SFRP1 Expression. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 28 28268231
2019 MiR-1180 from bone marrow MSCs promotes cell proliferation and glycolysis in ovarian cancer cells via SFRP1/Wnt pathway. Cancer cell international 27 30936781
2015 MiR-27a regulates Wnt/beta-catenin signaling through targeting SFRP1 in glioma. Neuroreport 27 26164457
2020 Increased expression of secreted frizzled related protein 1 (SFRP1) predicts ampullary adenocarcinoma recurrence. Scientific reports 26 32764696
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
2010 Secreted frizzled-related protein 1 (SFRP1) is highly upregulated in keratoconus epithelium: a novel finding highlighting a new potential focus for keratoconus research and treatment. Clinical & experimental ophthalmology 26 20447100
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
2009 Differential methylation pattern of ID4, SFRP1, and SHP1 between acute myeloid leukemia and chronic myeloid leukemia. Journal of Korean medical science 24 19543515
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
2018 sFRP1 exerts effects on gastric cancer cells through GSK3β/Rac1‑mediated restraint of TGFβ/Smad3 signaling. Oncology reports 22 30542739
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
2022 BMP-AKT-GSK3β Signaling Restores Hair Follicle Stem Cells Decrease Associated with Loss of Sfrp1. Stem cells (Dayton, Ohio) 20 35689817
2020 SFRP1 in Skin Tumor Initiation and Cancer Stem Cell Regulation with Potential Implications in Epithelial Cancers. Stem cell reports 20 31928951
2022 miR-26a-5p Suppresses Wnt/β-Catenin Signaling Pathway by Inhibiting DNMT3A-Mediated SFRP1 Methylation and Inhibits Cancer Stem Cell-Like Properties of NSCLC. Disease markers 19 35860691
2020 microRNA27a-3p mediates reduction of the Wnt antagonist sFRP-1 in systemic sclerosis. Epigenetics 19 32965161
2014 Immunohistochemical expression of SFRP1 and SFRP3 proteins in normal and malignant reproductive tissues of rats and humans. Applied immunohistochemistry & molecular morphology : AIMM 19 25046226
1995 Identification of fusion regulatory protein (FRP)-1/4F2 related molecules: cytoskeletal proteins are associated with FRP-1 molecules that regulate multinucleated giant cell formation of monocytes and HIV-induced cell fusion. Cell structure and function 19 8825068
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 Oncogenic miR-27a delivered by exosomes binds to SFRP1 and promotes angiogenesis in renal clear cell carcinoma. Molecular therapy. Nucleic acids 17 33738141
2019 SFRP1 inhibited the epithelial ovarian cancer through inhibiting Wnt/β-catenin signaling. Acta biochimica Polonica 17 31770484
2017 Methylation-associated silencing of SFRP1 gene in high-grade serous ovarian carcinomas. Annals of diagnostic pathology 17 29146058
1999 Suppression of FRP-1/CD98-mediated multinucleated giant cell and osteoclast formation by an anti-FRP-1/CD98 mAb, HBJ 127, that inhibits c-src expression. Cellular immunology 17 10222058
2025 FOS-driven inflammatory CAFs promote colorectal cancer liver metastasis via the SFRP1-FGFR2-HIF1 axis. Theranostics 16 40225580
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
2021 Glucocorticoid therapy suppresses Wnt signaling by reducing the ratio of serum Wnt3a to Wnt inhibitors, sFRP-1 and Wif-1. Clinical rheumatology 16 33420868
2020 Computational design of antagonist peptides based on the structure of secreted frizzled-related protein-1 (SFRP1) aiming to inhibit Wnt signaling pathway. Journal of biomolecular structure & dynamics 16 33155881
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

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