{"gene":"FSCN1","run_date":"2026-06-09T23:54:44","timeline":{"discoveries":[{"year":2016,"finding":"Zebrafish Fscn1a specifically interacts with TGF-β family type I receptors; its depletion disrupts the association between receptors and actin filaments, sequesters internalized receptors into clathrin-coated vesicles, and prevents their trafficking to early endosomes, thereby reducing Nodal signal transduction and endoderm formation. Fscn1 acts as a molecular linker between TGF-β family type I receptors and actin filaments.","method":"Co-immunoprecipitation, knockdown/knockout in zebrafish embryos, confocal imaging of receptor trafficking, genetic epistasis with Nodal signaling","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, in vivo KO/KD with defined cellular phenotype (endoderm loss), mechanistic dissection of trafficking step with multiple orthogonal methods in one rigorous study","pmids":["27545838"],"is_preprint":false},{"year":2019,"finding":"GRHL3 transcription factor directly activates FSCN1 expression in wound-front keratinocytes (ATAC-seq shows wound-induced chromatin accessibility near Fscn1 enriched for GRHL3 motifs). FSCN1 acts as a negative regulator of E-cadherin, relaxing keratinocyte-keratinocyte adherens junctions to promote collective migration and wound closure. Grhl3-cKO mice have reduced Fscn1 expression and impaired wound-front migration.","method":"ATAC-seq on wounded keratinocytes, conditional knockout mice (Grhl3-cKO), wound-healing assays, E-cadherin expression analysis, in vivo wound closure measurements","journal":"JCI insight","confidence":"High","confidence_rationale":"Tier 2 / Strong — ATAC-seq chromatin accessibility plus conditional KO with defined wound-migration phenotype and E-cadherin mechanistic link, multiple orthogonal methods","pmids":["34494554"],"is_preprint":false},{"year":2019,"finding":"FSCN1 physically interacts with AIMP1 and LTA4H in laryngeal squamous cell carcinoma cells, as identified by co-immunoprecipitation/mass spectrometry and validated by co-IP/western blotting and immunofluorescence co-localization. FSCN1-binding proteins are enriched in filopodium assembly-regulation and GTPase activity pathways.","method":"Co-immunoprecipitation followed by mass spectrometry, co-IP/western blot validation, immunofluorescence co-localization","journal":"Proteomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP/MS with western blot validation in single lab; binding partners identified but functional consequence of these specific interactions not fully reconstituted","pmids":["31287215"],"is_preprint":false},{"year":2019,"finding":"Mass spectrometry-based interactome of FSCN1 in LSCC cells identified 119 interacting proteins enriched in cell adhesion, glycolysis/gluconeogenesis, protein ubiquitination regulation, and rRNA processing pathways.","method":"Immunoprecipitation followed by mass spectrometry in two LSCC cell lines (Hep-2, TU-177)","journal":"IUBMB life","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single-lab MS interactome without functional validation of individual interactions; identifies candidate partners only","pmids":["31298480"],"is_preprint":false},{"year":2018,"finding":"FSCN1 physically interacts with Snail1 (Co-IP) and increases Snail1 protein levels in ovarian cancer cells, thereby promoting EMT (loss of E-cadherin, gain of vimentin). FSCN1 overexpression or depletion correspondingly modulates Snail1 and EMT markers.","method":"Co-immunoprecipitation, western blotting, RT-qPCR, transwell invasion assay, overexpression/knockdown in EOC cells","journal":"Cellular physiology and biochemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP with functional rescue experiments; single lab but two orthogonal methods (Co-IP + functional assays)","pmids":["30231243"],"is_preprint":false},{"year":2017,"finding":"EGF induces FSCN1 expression through activation of the MAPK pathway in triple-negative breast cancer cells, and elevated FSCN1 promotes cell migration and invasion.","method":"siRNA knockdown, western blotting, EGF stimulation with MAPK pathway inhibitors, migration/invasion assays","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab, pathway inhibition experiments with functional readout; MAPK→FSCN1 link established by pharmacological inhibition","pmids":["29142206"],"is_preprint":false},{"year":2018,"finding":"FSCN1 knockdown in doxorubicin-resistant HCC cells reduces drug resistance and is accompanied by decreased vimentin and increased E-cadherin, indicating FSCN1 promotes DOX resistance via EMT promotion. When EMT was suppressed by Twist knockdown, FSCN1 expression no longer affected DOX sensitivity, placing FSCN1 upstream of or within the Twist/EMT axis for resistance.","method":"siRNA knockdown, EMT marker western blotting, drug sensitivity assays, Twist knockdown epistasis experiment, hypoxia model","journal":"International journal of oncology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab, genetic epistasis (Twist-FSCN1) with functional drug-resistance phenotype; multiple experimental conditions","pmids":["29568938"],"is_preprint":false},{"year":2021,"finding":"ADORA2A-AS1 (lncRNA) competitively binds HuR (RNA-binding protein), preventing HuR from binding to FSCN1 mRNA and thereby decreasing FSCN1 transcript stability and expression. Reduced FSCN1 suppresses AKT pathway activation in HCC. Functional rescue assays show blockade of the FSCN1/AKT axis abrogates ADORA2A-AS1's tumor-suppressive effects.","method":"RNA pull-down, RNA immunoprecipitation, RNA stability assay, western blotting, qRT-PCR, xenograft models","journal":"Frontiers in oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNA pull-down + RIP + stability assay establish mechanism of HuR-mediated FSCN1 mRNA regulation; single lab","pmids":["34733789"],"is_preprint":false},{"year":2021,"finding":"LYAR (nucleolar protein) transcriptionally upregulates FSCN1 expression in colorectal cancer cells, as demonstrated by ChIP assay, gene reporter assay, and rescue experiments. FSCN1 knockdown inhibits subcutaneous tumorigenesis and downregulates FASN and SCD (fatty acid synthesis enzymes), linking FSCN1 to fatty acid metabolism.","method":"ChIP assay, luciferase reporter assay, microarray, rescue experiments, xenograft tumor model","journal":"Oxidative medicine and cellular longevity","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP + reporter assay establish direct transcriptional regulation; single lab with orthogonal methods","pmids":["35069968"],"is_preprint":false},{"year":2017,"finding":"SNAI2 directly binds a site in the FSCN1 promoter (verified by luciferase reporter assay) and its overexpression increases FSCN1 mRNA and protein in HNSC cells. FSCN1 overexpression reduces E-cadherin and Claudin-1 and increases Vimentin and N-cadherin, promoting EMT.","method":"Luciferase reporter assay, overexpression experiments, western blotting for EMT markers","journal":"Cell biology international","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — luciferase reporter confirms SNAI2 binding site, with functional EMT outcome; single lab, two methods","pmids":["28488774"],"is_preprint":false},{"year":2022,"finding":"FSCN1 binds to IGF-1R in lung adenocarcinoma cells (co-immunoprecipitation), activating PI3K-AKT and JAK-STAT signaling pathways, which promotes secretion of IL4 and M-CSF, inducing M2 polarization of macrophages via PTPRF upregulation.","method":"Co-immunoprecipitation, Seahorse metabolic analysis, western blotting, qRT-PCR, IVIS in vivo imaging","journal":"Cellular oncology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP identifying FSCN1-IGF1R interaction with downstream signaling validation; single lab","pmids":["36223033"],"is_preprint":false},{"year":2023,"finding":"FSCN1 binds to the pre-mRNA of PTK6 as an RNA-binding protein (RNA immunoprecipitation), downregulating PTK6 mRNA and protein levels to promote esophageal cancer progression via the AKT/GSK3β signaling pathway. A specific PTK6-T2 peptide blocks this FSCN1-pre-mRNA binding and reverses FSCN1's tumor-promoting effect.","method":"RNA immunoprecipitation, whole-genome expression sequencing, in vitro and in vivo tumor experiments","journal":"Frontiers in pharmacology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP establishes direct RNA-binding function of FSCN1; novel non-actin mechanism; single lab","pmids":["35401239"],"is_preprint":false},{"year":2023,"finding":"SYTL2 binds FSCN1 protein (co-immunoprecipitation) and inhibits its proteasome-mediated degradation, enhancing FSCN1 protein stability and thereby increasing pseudopodia formation and prostate cancer cell invasion/lymph node metastasis in vivo. FSCN1 knockdown rescues/reverses the oncogenic effect of SYTL2.","method":"Co-immunoprecipitation, protein stability assay, 3D migration model, popliteal lymph node metastasis in vivo model, rescue experiments","journal":"Journal of translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP + protein stability assay + in vivo rescue; single lab with multiple orthogonal methods","pmids":["37147713"],"is_preprint":false},{"year":2023,"finding":"NQO1 directly binds FSCN1 protein (immunoprecipitation) and stabilizes FSCN1, increasing migration and invasion in arsenic-transformed lung cells. Knockdown of MEG3 lncRNA upregulates NQO1, which stabilizes FSCN1; NQO1 knockdown reduces FSCN1-dependent migration/invasion, effects reversed by FSCN1 overexpression.","method":"Immunoprecipitation, western blotting, migration/invasion assays, rescue/epistasis experiments with MEG3, NQO1, FSCN1","journal":"American journal of cancer research","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct binding confirmed by IP with genetic epistasis; single lab, multiple orthogonal methods","pmids":["37424815"],"is_preprint":false},{"year":2023,"finding":"FSCN1 is a transcriptional target of β-catenin in ACC cells; FSCN1 inactivation (CRISPR/Cas9 KO or inhibitor G2-044) reduces filopodia, lamellipodia/ruffles, and focal adhesions, decreases cell invasion in Matrigel, and reduces metastasis formation in a zebrafish in vivo model.","method":"CRISPR/Cas9 knockout, pharmacological inhibition (G2-044), reporter assay for β-catenin binding, filopodia/focal adhesion imaging, zebrafish metastasis model","journal":"International journal of cancer","confidence":"High","confidence_rationale":"Tier 2 / Strong — CRISPR KO + pharmacological inhibition + reporter assay + in vivo zebrafish model; multiple orthogonal methods establishing FSCN1 role in cytoskeletal dynamics and invasion","pmids":["36971100"],"is_preprint":false},{"year":2023,"finding":"Oral small-molecule FSCN1 inhibitor NP-G2-044 impedes sprouting, migration, and filopodia formation in cultured endothelial cells and suppresses pathological ocular neovascularization (OIR and CNV mouse models) in vivo. Co-IP experiments reveal a mechanistic interaction between FSCN1 and angiogenesis-related factors.","method":"Transwell/wound scratch/tube formation/3D bead sprouting assays, rhodamine-phalloidin staining, in vivo OIR and CNV mouse models, pharmacokinetic HPLC-MS/MS, Co-IP","journal":"Journal of translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — pharmacological inhibition with multiple in vitro and in vivo functional readouts; single lab","pmids":["37596693"],"is_preprint":false},{"year":2023,"finding":"Ginsenoside Rb2 inhibits p300 acetyltransferase activity (thermodynamic, kinetic, and enzymatic experiments), reducing p300-mediated acetylation of spliceosome protein SF3A2 at lysine 10, which promotes alternative splicing of Fscn1 and upregulates Fscn1 expression, enhancing mitochondrial respiration to protect cardiomyocytes against ischemic injury.","method":"4D-label-free acetylomic analysis, co-immunoprecipitation, immunofluorescent staining, mitochondrial respiration (Seahorse), RNA-seq, site-specific mutation, shRNA interference, cellular thermal shift assay, surface plasmon resonance","journal":"Journal of advanced research","confidence":"High","confidence_rationale":"Tier 1 / Strong — enzymatic activity assay + SPR binding kinetics + mutagenesis + acetylomic proteomics establish p300→SF3A2(K10)→Fscn1 splicing axis; multiple orthogonal Tier 1 methods","pmids":["38101749"],"is_preprint":false},{"year":2024,"finding":"HPV16 E6/E7 oncogenes upregulate METTL14 and IGF2BP3, which mediate N6-methyladenosine (m6A) modification on FSCN1 mRNA to stabilize it and increase FSCN1 protein expression in cervical squamous cell carcinoma. Knockdown of E6/E7 or METTL14/IGF2BP3 suppresses FSCN1 expression and cancer cell proliferation/migration, effects reversed by FSCN1 overexpression.","method":"qRT-PCR, western blotting, MTT assay, flow cytometry, wound healing assay, tumor formation assay, gain/loss-of-function experiments","journal":"Clinical and experimental pharmacology & physiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — m6A modification mechanism established with genetic epistasis (rescue experiments); single lab","pmids":["38679464"],"is_preprint":false},{"year":2018,"finding":"FSCN1 promotes RCC cell invasion in vitro and metastasis in vivo; its expression is regulated by the PI3K/AKT/GSK-3β pathway (PI3K/AKT inhibitors or GSK-3β knockdown decrease FSCN1 expression). FSCN1 overexpression upregulates MMP9 and N-cadherin.","method":"PI3K/AKT inhibitor treatment, GSK-3β siRNA knockdown, western blotting, Matrigel invasion assay, orthotopic xenograft mice model","journal":"Journal of cellular physiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — pharmacological and genetic inhibition of upstream kinases with FSCN1 downstream readout; single lab with multiple methods","pmids":["29148041"],"is_preprint":false},{"year":2015,"finding":"FSCN1 loss-of-function (siRNA) suppresses migration and invasion of pituitary adenoma GH3 cells, accompanied by downregulation of Notch1 and DLL3 expression, suggesting FSCN1 acts upstream of Notch signaling in pituitary adenoma invasion.","method":"siRNA knockdown, transwell invasion assay, western blotting for Notch1/DLL3","journal":"Molecular and cellular endocrinology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single siRNA knockdown with pathway marker readout; limited mechanistic depth","pmids":["26522130"],"is_preprint":false},{"year":2025,"finding":"KDM7A demethylase reduces H3K9me2 and H3K27me2 enrichment at the Fscn1 promoter in medial prefrontal cortex neurons, thereby increasing Fscn1 transcription. Fscn1 knockdown in the mPFC reduces dendritic spine density, neuronal activity, and morphine-conditioned place preference memory consolidation, phenocopying Kdm7a knockdown.","method":"Nanopore direct RNA sequencing, H3K9me2/H3K27me2 ChIP at Fscn1 promoter, viral Fscn1 knockdown, dendritic spine analysis (morphology), behavioral CPP assay","journal":"Advanced science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP at specific locus + in vivo KD with behavioral and morphological phenotypes; single lab but multiple orthogonal methods","pmids":["39836528"],"is_preprint":false},{"year":2005,"finding":"FSCN1 expression in NT2 neuronal precursor cells is regulated by CBP (CREB-binding protein): siRNA depletion of CBP reduces FSCN1 mRNA and protein. FSCN1 is upregulated during retinoic acid-induced neuronal differentiation of NT2 cells, suggesting a role in neurite/growth cone formation consistent with its actin-bundling function.","method":"RNA interference (CBP siRNA), cDNA microarray, RT-qPCR, western blotting, retinoic acid differentiation model","journal":"Neuroscience letters","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, indirect regulation (CBP→FSCN1) without direct promoter binding evidence; functional consequence inferred from expression data","pmids":["15882811"],"is_preprint":false},{"year":2010,"finding":"miR-145, miR-133a, and miR-133b directly regulate FSCN1 by binding conserved sequences in the 3'UTR (luciferase reporter assay confirms two miR-145 target sites and one miR-133a/b site). FSCN1 loss-of-function inhibits esophageal squamous cell carcinoma cell growth and invasion.","method":"Luciferase reporter assay, gain-of-function miRNA transfection, siRNA FSCN1 knockdown, cell proliferation and invasion assays","journal":"International journal of cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Strong — luciferase assay confirming direct 3'UTR binding replicated across multiple cancer types and labs for miR-145/FSCN1 axis","pmids":["21351259"],"is_preprint":false},{"year":2021,"finding":"circFSCN1 (circular RNA from the FSCN1 locus) is highly expressed in the cytoplasm of mature dendritic cells; knockdown of circFSCN1 arrests DCs at an immature state, impairing their ability to activate T cells and enhancing regulatory T cell generation, preventing allograft rejection in a mouse heart transplantation model.","method":"circFSCN1 siRNA knockdown in bone marrow-derived DCs, flow cytometry for DC maturation, mixed lymphocyte reactions, in situ RNA hybridization, heterotopic allogeneic murine heart transplantation","journal":"The Journal of heart and lung transplantation","confidence":"Low","confidence_rationale":"Tier 3 / Weak — this describes circFSCN1 (a non-protein product of the locus), not the canonical FSCN1 protein; included only as context for the locus but does not report canonical protein mechanism","pmids":["34052126"],"is_preprint":false}],"current_model":"FSCN1 (Fascin-1) is an evolutionarily conserved actin-bundling protein that promotes cell migration, invasion, and filopodia/pseudopodia formation by crosslinking actin filaments; it also functions as a molecular linker between TGF-β family type I receptors and actin filaments to facilitate receptor trafficking from clathrin-coated vesicles to early endosomes (established in zebrafish), is transcriptionally activated by GRHL3, SNAI2, β-catenin, LYAR, and KDM7A (via histone demethylation at its promoter), physically interacts with IGF-1R, Snail1, NQO1, and SYTL2 (which protects it from proteasomal degradation), acts downstream of MAPK/EGF and PI3K/AKT/GSK-3β signaling, promotes EMT partly through Snail1 stabilization, and can act as an RNA-binding protein to suppress PTK6 mRNA; its expression is post-transcriptionally regulated by multiple miRNAs (including miR-145, miR-133a/b) targeting its 3'UTR and by m6A modification (METTL14/IGF2BP3-mediated mRNA stabilization), and pharmacological inhibition of its actin-bundling activity blocks angiogenesis and cancer invasion in vivo."},"narrative":{"mechanistic_narrative":"FSCN1 (Fascin-1) is an actin-organizing protein that drives cell migration, invasion, and metastasis by promoting filopodia, lamellipodia, and focal adhesion dynamics, a role demonstrated directly by CRISPR knockout and pharmacological inhibition that collapse these cytoskeletal structures and block invasion in vivo [PMID:36971100]. Beyond bundling actin, it acts as a molecular linker between TGF-β family type I receptors and actin filaments, where its loss traps internalized receptors in clathrin-coated vesicles, prevents their trafficking to early endosomes, and attenuates Nodal signaling and endoderm formation [PMID:27545838]. In epithelial contexts FSCN1 promotes epithelial-to-mesenchymal transition by negatively regulating E-cadherin and by physically interacting with and stabilizing the transcription factor Snail1 [PMID:34494554, PMID:30231243]. FSCN1 also exerts non-canonical RNA-binding activity, binding PTK6 pre-mRNA to suppress PTK6 and drive tumor progression through AKT/GSK3β signaling [PMID:35401239]. Its expression is controlled at multiple layers: transcriptionally by GRHL3, SNAI2, β-catenin, and the nucleolar protein LYAR [PMID:34494554, PMID:28488774, PMID:36971100, PMID:35069968], and by KDM7A-mediated histone demethylation at its promoter in neurons, where it supports dendritic spine density and morphine reward memory [PMID:39836528]; at the mRNA level by HuR-dependent stabilization, METTL14/IGF2BP3-mediated m6A modification, and direct 3'UTR targeting by miR-145 and miR-133a/b [PMID:34733789, PMID:38679464, PMID:21351259]; and at the protein level by binding partners SYTL2 and NQO1 that protect it from proteasomal degradation [PMID:37147713, PMID:37424815]. Small-molecule inhibition of its actin-bundling activity (NP-G2-044/G2-044) suppresses cancer invasion and pathological angiogenesis in vivo [PMID:36971100, PMID:37596693].","teleology":[{"year":2005,"claim":"Established a link between FSCN1 expression and neuronal differentiation, framing its actin-bundling role in growth cone/neurite formation.","evidence":"CBP siRNA depletion and retinoic acid differentiation in NT2 neuronal precursor cells with microarray/qPCR readout","pmids":["15882811"],"confidence":"Low","gaps":["No direct CBP promoter binding shown","Functional role in neurite formation inferred from expression, not tested"]},{"year":2010,"claim":"Defined post-transcriptional control of FSCN1 by identifying direct miRNA targeting of its 3'UTR, explaining how FSCN1 is silenced in non-invasive states.","evidence":"Luciferase reporter mapping of miR-145 and miR-133a/b 3'UTR sites plus FSCN1 knockdown invasion assays in esophageal cancer","pmids":["21351259"],"confidence":"Medium","gaps":["Does not address protein-level or transcriptional regulation","Endogenous miRNA dosage effects not quantified"]},{"year":2016,"claim":"Revealed a non-bundling, trafficking function: FSCN1 links TGF-β family type I receptors to actin to route them from clathrin-coated vesicles to early endosomes, controlling Nodal signaling.","evidence":"Reciprocal Co-IP, zebrafish knockdown/knockout, confocal receptor-trafficking imaging, genetic epistasis with Nodal","pmids":["27545838"],"confidence":"High","gaps":["Whether mammalian FSCN1 performs the identical trafficking step is untested","Structural basis of receptor-FSCN1 binding unresolved"]},{"year":2017,"claim":"Connected upstream signaling and transcription factors to FSCN1 induction, showing EGF/MAPK and SNAI2 drive its expression to promote migration and EMT.","evidence":"MAPK pathway inhibition with EGF stimulation in TNBC cells; luciferase mapping of SNAI2 binding to FSCN1 promoter in HNSC","pmids":["29142206","28488774"],"confidence":"Medium","gaps":["Direct vs indirect MAPK regulation not separated","Single-lab promoter reporter without endogenous ChIP for SNAI2"]},{"year":2018,"claim":"Placed FSCN1 within EMT and drug-resistance circuitry by showing it stabilizes Snail1, sits within the Twist/EMT axis, and lies downstream of PI3K/AKT/GSK-3β.","evidence":"Co-IP with Snail1 and functional EMT assays in ovarian cancer; Twist epistasis in DOX-resistant HCC; kinase inhibitor/GSK-3β knockdown in RCC with xenografts","pmids":["30231243","29568938","29148041"],"confidence":"Medium","gaps":["Mechanism of Snail1 stabilization by FSCN1 not defined","Direct vs indirect kinase regulation not resolved"]},{"year":2019,"claim":"Defined the GRHL3→FSCN1→E-cadherin axis in collective epithelial migration, extending FSCN1 function beyond cancer to physiological wound healing.","evidence":"ATAC-seq for GRHL3-motif accessibility, Grhl3 conditional knockout mice, wound-healing and E-cadherin analysis","pmids":["34494554"],"confidence":"High","gaps":["Direct GRHL3 binding to FSCN1 locus not shown by ChIP","How FSCN1 mechanistically relaxes adherens junctions unclear"]},{"year":2019,"claim":"Mapped the FSCN1 protein interactome, nominating filopodium-assembly, GTPase, adhesion, and metabolic partners as candidate effectors.","evidence":"Co-IP/mass spectrometry in laryngeal carcinoma cell lines with western/IF validation of AIMP1 and LTA4H","pmids":["31287215","31298480"],"confidence":"Medium","gaps":["Functional consequences of individual interactions not reconstituted","Interactome from single cancer type"]},{"year":2021,"claim":"Added a transcriptional and mRNA-stability layer to FSCN1 control via the nucleolar factor LYAR and the lncRNA/HuR axis, linking FSCN1 to fatty acid synthesis and AKT activation.","evidence":"ChIP/reporter assays for LYAR in colorectal cancer; RNA pull-down/RIP/stability assays for ADORA2A-AS1–HuR–FSCN1 in HCC with xenografts","pmids":["35069968","34733789"],"confidence":"Medium","gaps":["Mechanism linking FSCN1 to FASN/SCD not defined","Single-lab findings per axis"]},{"year":2022,"claim":"Extended FSCN1 signaling to the tumor microenvironment, showing it binds IGF-1R to drive PI3K-AKT/JAK-STAT activation and macrophage M2 polarization.","evidence":"Co-IP, Seahorse metabolic analysis, cytokine qRT-PCR, and in vivo imaging in lung adenocarcinoma","pmids":["36223033"],"confidence":"Medium","gaps":["Single Co-IP without reciprocal validation","Direct vs adaptor role of FSCN1 at IGF-1R unclear"]},{"year":2023,"claim":"Identified a non-canonical RNA-binding function and protein-level stabilizers, broadening FSCN1's mechanism beyond cytoskeletal bundling.","evidence":"RIP showing FSCN1 binding to PTK6 pre-mRNA in esophageal cancer; Co-IP/stability assays for SYTL2 and NQO1 with in vivo rescue in prostate and arsenic-transformed lung cells","pmids":["35401239","37147713","37424815"],"confidence":"Medium","gaps":["RNA-binding domain/motif of FSCN1 not mapped","How SYTL2/NQO1 block FSCN1 ubiquitination not defined"]},{"year":2023,"claim":"Validated FSCN1 as a pharmacological target downstream of β-catenin, with small-molecule inhibition collapsing cytoskeletal structures and suppressing invasion and pathological angiogenesis.","evidence":"CRISPR KO plus G2-044 inhibitor and zebrafish metastasis model; NP-G2-044 in endothelial assays and OIR/CNV mouse models","pmids":["36971100","37596693"],"confidence":"High","gaps":["Inhibitor selectivity over fascin paralogs not addressed in timeline","Angiogenesis interaction partners not fully defined"]},{"year":2023,"claim":"Connected acetylation-controlled splicing to Fscn1 expression, showing a p300→SF3A2(K10)→Fscn1 splicing axis with a cardioprotective, mitochondrial-respiration outcome.","evidence":"Acetylomic proteomics, SPR/CETSA binding kinetics, site-specific mutagenesis, and Seahorse in cardiomyocytes treated with ginsenoside Rb2","pmids":["38101749"],"confidence":"High","gaps":["Which Fscn1 isoform mediates mitochondrial protection not specified","Direct role of FSCN1 protein in respiration mechanism unresolved"]},{"year":2024,"claim":"Established m6A-dependent stabilization of FSCN1 mRNA by viral oncogenes, adding epitranscriptomic regulation to its control.","evidence":"HPV16 E6/E7 and METTL14/IGF2BP3 knockdown with rescue in cervical carcinoma cells","pmids":["38679464"],"confidence":"Medium","gaps":["m6A site on FSCN1 mRNA not mapped","Single-lab study"]},{"year":2025,"claim":"Demonstrated an epigenetic-neuronal role: KDM7A demethylation activates Fscn1 to support dendritic spine density and drug-reward memory, extending FSCN1 function into CNS plasticity.","evidence":"Locus-specific H3K9me2/H3K27me2 ChIP, viral Fscn1 knockdown, spine morphology, and conditioned place preference behavior in mPFC neurons","pmids":["39836528"],"confidence":"Medium","gaps":["How actin-bundling drives spine density mechanistically not dissected","KDM7A binding to Fscn1 promoter inferred from demethylation only"]},{"year":null,"claim":"How FSCN1's distinct activities — actin bundling, receptor trafficking, RNA binding, and partner-controlled stability — are coordinated within a single cell and whether they share a common structural determinant remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model integrating actin-bundling and RNA-binding functions","Regulatory hierarchy among transcriptional, m6A, miRNA, and protein-stability controls not established","Tissue-specific selection among FSCN1's functions unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,14,15]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[11]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[14,15]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[11]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,10,18]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[1,20]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[14,17]}],"complexes":[],"partners":["TGFBR1","SNAI1","IGF1R","SYTL2","NQO1","AIMP1","LTA4H","HUR"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q16658","full_name":"Fascin","aliases":["55 kDa actin-bundling protein","Singed-like protein","p55"],"length_aa":493,"mass_kda":54.5,"function":"Actin-binding protein that contains 2 major actin binding sites (PubMed:21685497, PubMed:23184945). Organizes filamentous actin into parallel bundles (PubMed:20393565, PubMed:21685497, PubMed:23184945). Plays a role in the organization of actin filament bundles and the formation of microspikes, membrane ruffles, and stress fibers (PubMed:22155786). Important for the formation of a diverse set of cell protrusions, such as filopodia, and for cell motility and migration (PubMed:20393565, PubMed:21685497, PubMed:23184945). 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library.","date":"2009","source":"Molecular biology reports","url":"https://pubmed.ncbi.nlm.nih.gov/19688270","citation_count":7,"is_preprint":false},{"pmid":"35595956","id":"PMC_35595956","title":"MicroRNA-133 suppresses cell viability and migration of rheumatoid arthritis fibroblast-like synoviocytes by down-regulation of MET, EGFR, and FSCN1 expression.","date":"2022","source":"Molecular and cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/35595956","citation_count":7,"is_preprint":false},{"pmid":"39836528","id":"PMC_39836528","title":"The Histone Lysine Demethylase KDM7A Contributes to Reward Memory via Fscn1-Induced Synaptic Plasticity in the Medial Prefrontal Cortex.","date":"2025","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/39836528","citation_count":7,"is_preprint":false},{"pmid":"33928608","id":"PMC_33928608","title":"LncRNA PRNCR1 aggravates the malignancy of oral squamous cell carcinoma by regulating miR-326/FSCN1 axis.","date":"2021","source":"European review for medical and pharmacological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/33928608","citation_count":7,"is_preprint":false},{"pmid":"30769782","id":"PMC_30769782","title":"Biomarker Analysis of Orally Dosed, Dual Active, Matrix Metalloproteinase (MMP)-2 and MMP-9 Inhibitor, AQU-118, in the Spinal Nerve Ligation (SNL) Rat Model of Neuropathic Pain.","date":"2019","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/30769782","citation_count":7,"is_preprint":false},{"pmid":"36927659","id":"PMC_36927659","title":"The role and regulatory mechanism of FSCN1 in breast tumorigenesis and progression.","date":"2023","source":"Yi chuan = Hereditas","url":"https://pubmed.ncbi.nlm.nih.gov/36927659","citation_count":6,"is_preprint":false},{"pmid":"35178306","id":"PMC_35178306","title":"Transcriptome analysis reveals the potential biological function of FSCN1 in HeLa cervical cancer cells.","date":"2022","source":"PeerJ","url":"https://pubmed.ncbi.nlm.nih.gov/35178306","citation_count":6,"is_preprint":false},{"pmid":"36960218","id":"PMC_36960218","title":"LncRNA PTOV1-AS2 Promotes Colon Cancer Progression through the miR-145-5p/FSCN1 Axis.","date":"2023","source":"Journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36960218","citation_count":6,"is_preprint":false},{"pmid":"37424815","id":"PMC_37424815","title":"Loss of MEG3 contributes to the enhanced migration and invasion in arsenic-induced carcinogenesis through NQO1/FSCN1 pathway.","date":"2023","source":"American journal of cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/37424815","citation_count":6,"is_preprint":false},{"pmid":"25556494","id":"PMC_25556494","title":"Solanum Nigrum polysaccharide (SNL) extract effects in transplanted tumor-bearing mice--erythrocyte membrane fluidity and blocking of functions.","date":"2014","source":"Asian Pacific journal of cancer prevention : APJCP","url":"https://pubmed.ncbi.nlm.nih.gov/25556494","citation_count":6,"is_preprint":false},{"pmid":"35401239","id":"PMC_35401239","title":"FSCN1 Promotes Esophageal Carcinoma Progression Through Downregulating PTK6 via its RNA-Binding Protein Effect.","date":"2022","source":"Frontiers in pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/35401239","citation_count":5,"is_preprint":false},{"pmid":"35367835","id":"PMC_35367835","title":"Role of FSCN1 in the tumor microenvironment of lung squamous cell carcinoma.","date":"2022","source":"Immunobiology","url":"https://pubmed.ncbi.nlm.nih.gov/35367835","citation_count":5,"is_preprint":false},{"pmid":"39035266","id":"PMC_39035266","title":"Targeting MetaLnc9/miR-143/FSCN1 axis inhibits oxidative stress and myofibroblast transdifferentiation in oral submucous fibrosis.","date":"2024","source":"Journal of dental sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39035266","citation_count":5,"is_preprint":false},{"pmid":"32654289","id":"PMC_32654289","title":"Long intergenic non-coding RNA 00337 confers progression of esophageal cancer by mediating microrna-145-dependent fscn1.","date":"2020","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/32654289","citation_count":5,"is_preprint":false},{"pmid":"33794251","id":"PMC_33794251","title":"WITHDRAWN: Exosomes from microRNA-145-5p-modified HUCB-MSCs attenuate CCl4-induced hepatic fibrosis via down-regulating FSCN1 expression.","date":"2021","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/33794251","citation_count":5,"is_preprint":false},{"pmid":"37832352","id":"PMC_37832352","title":"FSCN1 and epithelial mesenchymal transformation transcription factor expression in human pancreatic intraepithelial neoplasia and ductal adenocarcinoma.","date":"2023","source":"Pathology, research and practice","url":"https://pubmed.ncbi.nlm.nih.gov/37832352","citation_count":4,"is_preprint":false},{"pmid":"37211600","id":"PMC_37211600","title":"Electroacupuncture inhibits dendritic spine remodeling through the srGAP3-Rac1 signaling pathway in rats with SNL.","date":"2023","source":"Biological research","url":"https://pubmed.ncbi.nlm.nih.gov/37211600","citation_count":4,"is_preprint":false},{"pmid":"38679464","id":"PMC_38679464","title":"N6-methyladenosine methylation on FSCN1 mediated by METTL14/IGF2BP3 contributes to human papillomavirus type 16-infected cervical squamous cell carcinoma.","date":"2024","source":"Clinical and experimental pharmacology & physiology","url":"https://pubmed.ncbi.nlm.nih.gov/38679464","citation_count":4,"is_preprint":false},{"pmid":"33397549","id":"PMC_33397549","title":"Enhanced Suppression of Disulfide Cross-Linking Micelles Nanocarriers Loaded miR-145 Delivering System via Down-Regulation of MYC and FSCN1 in Colon Cancer Cells.","date":"2020","source":"Journal of biomedical nanotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/33397549","citation_count":4,"is_preprint":false},{"pmid":"40794739","id":"PMC_40794739","title":"The SNL Histone Deacetylase-Binding Factor GmHE13 Is a Novel Regulator of Soybean Hypocotyl Elongation.","date":"2025","source":"Plant biotechnology journal","url":"https://pubmed.ncbi.nlm.nih.gov/40794739","citation_count":3,"is_preprint":false},{"pmid":"33081806","id":"PMC_33081806","title":"Correction to: The role of microRNA-133b and its target gene FSCN1 in gastric cancer.","date":"2020","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/33081806","citation_count":3,"is_preprint":false},{"pmid":"35602576","id":"PMC_35602576","title":"Study on the Function and Mechanism of miR-585-3p Inhibiting the Progression of Ovarian Cancer Cells by Targeting FSCN1 to Block the MAPK Signaling Pathway.","date":"2022","source":"Analytical cellular pathology (Amsterdam)","url":"https://pubmed.ncbi.nlm.nih.gov/35602576","citation_count":2,"is_preprint":false},{"pmid":"38587571","id":"PMC_38587571","title":"The association of FSCN1 (rs852479, rs1640233) and HOTAIR (rs920778) polymorphisms with the risk of breast cancer in Egyptian women.","date":"2024","source":"Molecular biology reports","url":"https://pubmed.ncbi.nlm.nih.gov/38587571","citation_count":2,"is_preprint":false},{"pmid":"39618922","id":"PMC_39618922","title":"FSCN1 is a Potential Therapeutic Target for Atherosclerosis Revealed by Single-Cell and Bulk RNA Sequencing.","date":"2024","source":"Journal of inflammation research","url":"https://pubmed.ncbi.nlm.nih.gov/39618922","citation_count":1,"is_preprint":false},{"pmid":"20377687","id":"PMC_20377687","title":"Identification and gene mapping of a novel mutant supernumerary lodicules (snl) in rice.","date":"2010","source":"Journal of integrative plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/20377687","citation_count":1,"is_preprint":false},{"pmid":"38964493","id":"PMC_38964493","title":"The FSCN1 gene rs2966447 variant is associated with increased serum fascin-1 levels and breast cancer susceptibility.","date":"2024","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/38964493","citation_count":1,"is_preprint":false},{"pmid":"37634036","id":"PMC_37634036","title":"Comparative proteome and serum analysis identified FSCN1 as a marker of abiraterone resistance in castration-resistant prostate cancer.","date":"2023","source":"Prostate cancer and prostatic diseases","url":"https://pubmed.ncbi.nlm.nih.gov/37634036","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":54389,"output_tokens":6322,"usd":0.128998,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":15116,"output_tokens":4746,"usd":0.097115,"stage2_stop_reason":"end_turn"},"total_usd":0.226113,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"Zebrafish Fscn1a specifically interacts with TGF-β family type I receptors; its depletion disrupts the association between receptors and actin filaments, sequesters internalized receptors into clathrin-coated vesicles, and prevents their trafficking to early endosomes, thereby reducing Nodal signal transduction and endoderm formation. Fscn1 acts as a molecular linker between TGF-β family type I receptors and actin filaments.\",\n      \"method\": \"Co-immunoprecipitation, knockdown/knockout in zebrafish embryos, confocal imaging of receptor trafficking, genetic epistasis with Nodal signaling\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, in vivo KO/KD with defined cellular phenotype (endoderm loss), mechanistic dissection of trafficking step with multiple orthogonal methods in one rigorous study\",\n      \"pmids\": [\"27545838\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"GRHL3 transcription factor directly activates FSCN1 expression in wound-front keratinocytes (ATAC-seq shows wound-induced chromatin accessibility near Fscn1 enriched for GRHL3 motifs). FSCN1 acts as a negative regulator of E-cadherin, relaxing keratinocyte-keratinocyte adherens junctions to promote collective migration and wound closure. Grhl3-cKO mice have reduced Fscn1 expression and impaired wound-front migration.\",\n      \"method\": \"ATAC-seq on wounded keratinocytes, conditional knockout mice (Grhl3-cKO), wound-healing assays, E-cadherin expression analysis, in vivo wound closure measurements\",\n      \"journal\": \"JCI insight\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — ATAC-seq chromatin accessibility plus conditional KO with defined wound-migration phenotype and E-cadherin mechanistic link, multiple orthogonal methods\",\n      \"pmids\": [\"34494554\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"FSCN1 physically interacts with AIMP1 and LTA4H in laryngeal squamous cell carcinoma cells, as identified by co-immunoprecipitation/mass spectrometry and validated by co-IP/western blotting and immunofluorescence co-localization. FSCN1-binding proteins are enriched in filopodium assembly-regulation and GTPase activity pathways.\",\n      \"method\": \"Co-immunoprecipitation followed by mass spectrometry, co-IP/western blot validation, immunofluorescence co-localization\",\n      \"journal\": \"Proteomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP/MS with western blot validation in single lab; binding partners identified but functional consequence of these specific interactions not fully reconstituted\",\n      \"pmids\": [\"31287215\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Mass spectrometry-based interactome of FSCN1 in LSCC cells identified 119 interacting proteins enriched in cell adhesion, glycolysis/gluconeogenesis, protein ubiquitination regulation, and rRNA processing pathways.\",\n      \"method\": \"Immunoprecipitation followed by mass spectrometry in two LSCC cell lines (Hep-2, TU-177)\",\n      \"journal\": \"IUBMB life\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single-lab MS interactome without functional validation of individual interactions; identifies candidate partners only\",\n      \"pmids\": [\"31298480\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"FSCN1 physically interacts with Snail1 (Co-IP) and increases Snail1 protein levels in ovarian cancer cells, thereby promoting EMT (loss of E-cadherin, gain of vimentin). FSCN1 overexpression or depletion correspondingly modulates Snail1 and EMT markers.\",\n      \"method\": \"Co-immunoprecipitation, western blotting, RT-qPCR, transwell invasion assay, overexpression/knockdown in EOC cells\",\n      \"journal\": \"Cellular physiology and biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP with functional rescue experiments; single lab but two orthogonal methods (Co-IP + functional assays)\",\n      \"pmids\": [\"30231243\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"EGF induces FSCN1 expression through activation of the MAPK pathway in triple-negative breast cancer cells, and elevated FSCN1 promotes cell migration and invasion.\",\n      \"method\": \"siRNA knockdown, western blotting, EGF stimulation with MAPK pathway inhibitors, migration/invasion assays\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab, pathway inhibition experiments with functional readout; MAPK→FSCN1 link established by pharmacological inhibition\",\n      \"pmids\": [\"29142206\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"FSCN1 knockdown in doxorubicin-resistant HCC cells reduces drug resistance and is accompanied by decreased vimentin and increased E-cadherin, indicating FSCN1 promotes DOX resistance via EMT promotion. When EMT was suppressed by Twist knockdown, FSCN1 expression no longer affected DOX sensitivity, placing FSCN1 upstream of or within the Twist/EMT axis for resistance.\",\n      \"method\": \"siRNA knockdown, EMT marker western blotting, drug sensitivity assays, Twist knockdown epistasis experiment, hypoxia model\",\n      \"journal\": \"International journal of oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab, genetic epistasis (Twist-FSCN1) with functional drug-resistance phenotype; multiple experimental conditions\",\n      \"pmids\": [\"29568938\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"ADORA2A-AS1 (lncRNA) competitively binds HuR (RNA-binding protein), preventing HuR from binding to FSCN1 mRNA and thereby decreasing FSCN1 transcript stability and expression. Reduced FSCN1 suppresses AKT pathway activation in HCC. Functional rescue assays show blockade of the FSCN1/AKT axis abrogates ADORA2A-AS1's tumor-suppressive effects.\",\n      \"method\": \"RNA pull-down, RNA immunoprecipitation, RNA stability assay, western blotting, qRT-PCR, xenograft models\",\n      \"journal\": \"Frontiers in oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNA pull-down + RIP + stability assay establish mechanism of HuR-mediated FSCN1 mRNA regulation; single lab\",\n      \"pmids\": [\"34733789\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"LYAR (nucleolar protein) transcriptionally upregulates FSCN1 expression in colorectal cancer cells, as demonstrated by ChIP assay, gene reporter assay, and rescue experiments. FSCN1 knockdown inhibits subcutaneous tumorigenesis and downregulates FASN and SCD (fatty acid synthesis enzymes), linking FSCN1 to fatty acid metabolism.\",\n      \"method\": \"ChIP assay, luciferase reporter assay, microarray, rescue experiments, xenograft tumor model\",\n      \"journal\": \"Oxidative medicine and cellular longevity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP + reporter assay establish direct transcriptional regulation; single lab with orthogonal methods\",\n      \"pmids\": [\"35069968\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"SNAI2 directly binds a site in the FSCN1 promoter (verified by luciferase reporter assay) and its overexpression increases FSCN1 mRNA and protein in HNSC cells. FSCN1 overexpression reduces E-cadherin and Claudin-1 and increases Vimentin and N-cadherin, promoting EMT.\",\n      \"method\": \"Luciferase reporter assay, overexpression experiments, western blotting for EMT markers\",\n      \"journal\": \"Cell biology international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — luciferase reporter confirms SNAI2 binding site, with functional EMT outcome; single lab, two methods\",\n      \"pmids\": [\"28488774\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"FSCN1 binds to IGF-1R in lung adenocarcinoma cells (co-immunoprecipitation), activating PI3K-AKT and JAK-STAT signaling pathways, which promotes secretion of IL4 and M-CSF, inducing M2 polarization of macrophages via PTPRF upregulation.\",\n      \"method\": \"Co-immunoprecipitation, Seahorse metabolic analysis, western blotting, qRT-PCR, IVIS in vivo imaging\",\n      \"journal\": \"Cellular oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP identifying FSCN1-IGF1R interaction with downstream signaling validation; single lab\",\n      \"pmids\": [\"36223033\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"FSCN1 binds to the pre-mRNA of PTK6 as an RNA-binding protein (RNA immunoprecipitation), downregulating PTK6 mRNA and protein levels to promote esophageal cancer progression via the AKT/GSK3β signaling pathway. A specific PTK6-T2 peptide blocks this FSCN1-pre-mRNA binding and reverses FSCN1's tumor-promoting effect.\",\n      \"method\": \"RNA immunoprecipitation, whole-genome expression sequencing, in vitro and in vivo tumor experiments\",\n      \"journal\": \"Frontiers in pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP establishes direct RNA-binding function of FSCN1; novel non-actin mechanism; single lab\",\n      \"pmids\": [\"35401239\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SYTL2 binds FSCN1 protein (co-immunoprecipitation) and inhibits its proteasome-mediated degradation, enhancing FSCN1 protein stability and thereby increasing pseudopodia formation and prostate cancer cell invasion/lymph node metastasis in vivo. FSCN1 knockdown rescues/reverses the oncogenic effect of SYTL2.\",\n      \"method\": \"Co-immunoprecipitation, protein stability assay, 3D migration model, popliteal lymph node metastasis in vivo model, rescue experiments\",\n      \"journal\": \"Journal of translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP + protein stability assay + in vivo rescue; single lab with multiple orthogonal methods\",\n      \"pmids\": [\"37147713\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"NQO1 directly binds FSCN1 protein (immunoprecipitation) and stabilizes FSCN1, increasing migration and invasion in arsenic-transformed lung cells. Knockdown of MEG3 lncRNA upregulates NQO1, which stabilizes FSCN1; NQO1 knockdown reduces FSCN1-dependent migration/invasion, effects reversed by FSCN1 overexpression.\",\n      \"method\": \"Immunoprecipitation, western blotting, migration/invasion assays, rescue/epistasis experiments with MEG3, NQO1, FSCN1\",\n      \"journal\": \"American journal of cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct binding confirmed by IP with genetic epistasis; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"37424815\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"FSCN1 is a transcriptional target of β-catenin in ACC cells; FSCN1 inactivation (CRISPR/Cas9 KO or inhibitor G2-044) reduces filopodia, lamellipodia/ruffles, and focal adhesions, decreases cell invasion in Matrigel, and reduces metastasis formation in a zebrafish in vivo model.\",\n      \"method\": \"CRISPR/Cas9 knockout, pharmacological inhibition (G2-044), reporter assay for β-catenin binding, filopodia/focal adhesion imaging, zebrafish metastasis model\",\n      \"journal\": \"International journal of cancer\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — CRISPR KO + pharmacological inhibition + reporter assay + in vivo zebrafish model; multiple orthogonal methods establishing FSCN1 role in cytoskeletal dynamics and invasion\",\n      \"pmids\": [\"36971100\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Oral small-molecule FSCN1 inhibitor NP-G2-044 impedes sprouting, migration, and filopodia formation in cultured endothelial cells and suppresses pathological ocular neovascularization (OIR and CNV mouse models) in vivo. Co-IP experiments reveal a mechanistic interaction between FSCN1 and angiogenesis-related factors.\",\n      \"method\": \"Transwell/wound scratch/tube formation/3D bead sprouting assays, rhodamine-phalloidin staining, in vivo OIR and CNV mouse models, pharmacokinetic HPLC-MS/MS, Co-IP\",\n      \"journal\": \"Journal of translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — pharmacological inhibition with multiple in vitro and in vivo functional readouts; single lab\",\n      \"pmids\": [\"37596693\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Ginsenoside Rb2 inhibits p300 acetyltransferase activity (thermodynamic, kinetic, and enzymatic experiments), reducing p300-mediated acetylation of spliceosome protein SF3A2 at lysine 10, which promotes alternative splicing of Fscn1 and upregulates Fscn1 expression, enhancing mitochondrial respiration to protect cardiomyocytes against ischemic injury.\",\n      \"method\": \"4D-label-free acetylomic analysis, co-immunoprecipitation, immunofluorescent staining, mitochondrial respiration (Seahorse), RNA-seq, site-specific mutation, shRNA interference, cellular thermal shift assay, surface plasmon resonance\",\n      \"journal\": \"Journal of advanced research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — enzymatic activity assay + SPR binding kinetics + mutagenesis + acetylomic proteomics establish p300→SF3A2(K10)→Fscn1 splicing axis; multiple orthogonal Tier 1 methods\",\n      \"pmids\": [\"38101749\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"HPV16 E6/E7 oncogenes upregulate METTL14 and IGF2BP3, which mediate N6-methyladenosine (m6A) modification on FSCN1 mRNA to stabilize it and increase FSCN1 protein expression in cervical squamous cell carcinoma. Knockdown of E6/E7 or METTL14/IGF2BP3 suppresses FSCN1 expression and cancer cell proliferation/migration, effects reversed by FSCN1 overexpression.\",\n      \"method\": \"qRT-PCR, western blotting, MTT assay, flow cytometry, wound healing assay, tumor formation assay, gain/loss-of-function experiments\",\n      \"journal\": \"Clinical and experimental pharmacology & physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — m6A modification mechanism established with genetic epistasis (rescue experiments); single lab\",\n      \"pmids\": [\"38679464\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"FSCN1 promotes RCC cell invasion in vitro and metastasis in vivo; its expression is regulated by the PI3K/AKT/GSK-3β pathway (PI3K/AKT inhibitors or GSK-3β knockdown decrease FSCN1 expression). FSCN1 overexpression upregulates MMP9 and N-cadherin.\",\n      \"method\": \"PI3K/AKT inhibitor treatment, GSK-3β siRNA knockdown, western blotting, Matrigel invasion assay, orthotopic xenograft mice model\",\n      \"journal\": \"Journal of cellular physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — pharmacological and genetic inhibition of upstream kinases with FSCN1 downstream readout; single lab with multiple methods\",\n      \"pmids\": [\"29148041\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"FSCN1 loss-of-function (siRNA) suppresses migration and invasion of pituitary adenoma GH3 cells, accompanied by downregulation of Notch1 and DLL3 expression, suggesting FSCN1 acts upstream of Notch signaling in pituitary adenoma invasion.\",\n      \"method\": \"siRNA knockdown, transwell invasion assay, western blotting for Notch1/DLL3\",\n      \"journal\": \"Molecular and cellular endocrinology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single siRNA knockdown with pathway marker readout; limited mechanistic depth\",\n      \"pmids\": [\"26522130\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"KDM7A demethylase reduces H3K9me2 and H3K27me2 enrichment at the Fscn1 promoter in medial prefrontal cortex neurons, thereby increasing Fscn1 transcription. Fscn1 knockdown in the mPFC reduces dendritic spine density, neuronal activity, and morphine-conditioned place preference memory consolidation, phenocopying Kdm7a knockdown.\",\n      \"method\": \"Nanopore direct RNA sequencing, H3K9me2/H3K27me2 ChIP at Fscn1 promoter, viral Fscn1 knockdown, dendritic spine analysis (morphology), behavioral CPP assay\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP at specific locus + in vivo KD with behavioral and morphological phenotypes; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"39836528\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"FSCN1 expression in NT2 neuronal precursor cells is regulated by CBP (CREB-binding protein): siRNA depletion of CBP reduces FSCN1 mRNA and protein. FSCN1 is upregulated during retinoic acid-induced neuronal differentiation of NT2 cells, suggesting a role in neurite/growth cone formation consistent with its actin-bundling function.\",\n      \"method\": \"RNA interference (CBP siRNA), cDNA microarray, RT-qPCR, western blotting, retinoic acid differentiation model\",\n      \"journal\": \"Neuroscience letters\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, indirect regulation (CBP→FSCN1) without direct promoter binding evidence; functional consequence inferred from expression data\",\n      \"pmids\": [\"15882811\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"miR-145, miR-133a, and miR-133b directly regulate FSCN1 by binding conserved sequences in the 3'UTR (luciferase reporter assay confirms two miR-145 target sites and one miR-133a/b site). FSCN1 loss-of-function inhibits esophageal squamous cell carcinoma cell growth and invasion.\",\n      \"method\": \"Luciferase reporter assay, gain-of-function miRNA transfection, siRNA FSCN1 knockdown, cell proliferation and invasion assays\",\n      \"journal\": \"International journal of cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Strong — luciferase assay confirming direct 3'UTR binding replicated across multiple cancer types and labs for miR-145/FSCN1 axis\",\n      \"pmids\": [\"21351259\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"circFSCN1 (circular RNA from the FSCN1 locus) is highly expressed in the cytoplasm of mature dendritic cells; knockdown of circFSCN1 arrests DCs at an immature state, impairing their ability to activate T cells and enhancing regulatory T cell generation, preventing allograft rejection in a mouse heart transplantation model.\",\n      \"method\": \"circFSCN1 siRNA knockdown in bone marrow-derived DCs, flow cytometry for DC maturation, mixed lymphocyte reactions, in situ RNA hybridization, heterotopic allogeneic murine heart transplantation\",\n      \"journal\": \"The Journal of heart and lung transplantation\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — this describes circFSCN1 (a non-protein product of the locus), not the canonical FSCN1 protein; included only as context for the locus but does not report canonical protein mechanism\",\n      \"pmids\": [\"34052126\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"FSCN1 (Fascin-1) is an evolutionarily conserved actin-bundling protein that promotes cell migration, invasion, and filopodia/pseudopodia formation by crosslinking actin filaments; it also functions as a molecular linker between TGF-β family type I receptors and actin filaments to facilitate receptor trafficking from clathrin-coated vesicles to early endosomes (established in zebrafish), is transcriptionally activated by GRHL3, SNAI2, β-catenin, LYAR, and KDM7A (via histone demethylation at its promoter), physically interacts with IGF-1R, Snail1, NQO1, and SYTL2 (which protects it from proteasomal degradation), acts downstream of MAPK/EGF and PI3K/AKT/GSK-3β signaling, promotes EMT partly through Snail1 stabilization, and can act as an RNA-binding protein to suppress PTK6 mRNA; its expression is post-transcriptionally regulated by multiple miRNAs (including miR-145, miR-133a/b) targeting its 3'UTR and by m6A modification (METTL14/IGF2BP3-mediated mRNA stabilization), and pharmacological inhibition of its actin-bundling activity blocks angiogenesis and cancer invasion in vivo.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"FSCN1 (Fascin-1) is an actin-organizing protein that drives cell migration, invasion, and metastasis by promoting filopodia, lamellipodia, and focal adhesion dynamics, a role demonstrated directly by CRISPR knockout and pharmacological inhibition that collapse these cytoskeletal structures and block invasion in vivo [#14]. Beyond bundling actin, it acts as a molecular linker between TGF-\\u03b2 family type I receptors and actin filaments, where its loss traps internalized receptors in clathrin-coated vesicles, prevents their trafficking to early endosomes, and attenuates Nodal signaling and endoderm formation [#0]. In epithelial contexts FSCN1 promotes epithelial-to-mesenchymal transition by negatively regulating E-cadherin and by physically interacting with and stabilizing the transcription factor Snail1 [#1, #4]. FSCN1 also exerts non-canonical RNA-binding activity, binding PTK6 pre-mRNA to suppress PTK6 and drive tumor progression through AKT/GSK3\\u03b2 signaling [#11]. Its expression is controlled at multiple layers: transcriptionally by GRHL3, SNAI2, \\u03b2-catenin, and the nucleolar protein LYAR [#1, #9, #14, #8], and by KDM7A-mediated histone demethylation at its promoter in neurons, where it supports dendritic spine density and morphine reward memory [#20]; at the mRNA level by HuR-dependent stabilization, METTL14/IGF2BP3-mediated m6A modification, and direct 3'UTR targeting by miR-145 and miR-133a/b [#7, #17, #22]; and at the protein level by binding partners SYTL2 and NQO1 that protect it from proteasomal degradation [#12, #13]. Small-molecule inhibition of its actin-bundling activity (NP-G2-044/G2-044) suppresses cancer invasion and pathological angiogenesis in vivo [#14, #15].\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Established a link between FSCN1 expression and neuronal differentiation, framing its actin-bundling role in growth cone/neurite formation.\",\n      \"evidence\": \"CBP siRNA depletion and retinoic acid differentiation in NT2 neuronal precursor cells with microarray/qPCR readout\",\n      \"pmids\": [\"15882811\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct CBP promoter binding shown\", \"Functional role in neurite formation inferred from expression, not tested\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Defined post-transcriptional control of FSCN1 by identifying direct miRNA targeting of its 3'UTR, explaining how FSCN1 is silenced in non-invasive states.\",\n      \"evidence\": \"Luciferase reporter mapping of miR-145 and miR-133a/b 3'UTR sites plus FSCN1 knockdown invasion assays in esophageal cancer\",\n      \"pmids\": [\"21351259\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not address protein-level or transcriptional regulation\", \"Endogenous miRNA dosage effects not quantified\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Revealed a non-bundling, trafficking function: FSCN1 links TGF-\\u03b2 family type I receptors to actin to route them from clathrin-coated vesicles to early endosomes, controlling Nodal signaling.\",\n      \"evidence\": \"Reciprocal Co-IP, zebrafish knockdown/knockout, confocal receptor-trafficking imaging, genetic epistasis with Nodal\",\n      \"pmids\": [\"27545838\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether mammalian FSCN1 performs the identical trafficking step is untested\", \"Structural basis of receptor-FSCN1 binding unresolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Connected upstream signaling and transcription factors to FSCN1 induction, showing EGF/MAPK and SNAI2 drive its expression to promote migration and EMT.\",\n      \"evidence\": \"MAPK pathway inhibition with EGF stimulation in TNBC cells; luciferase mapping of SNAI2 binding to FSCN1 promoter in HNSC\",\n      \"pmids\": [\"29142206\", \"28488774\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs indirect MAPK regulation not separated\", \"Single-lab promoter reporter without endogenous ChIP for SNAI2\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Placed FSCN1 within EMT and drug-resistance circuitry by showing it stabilizes Snail1, sits within the Twist/EMT axis, and lies downstream of PI3K/AKT/GSK-3\\u03b2.\",\n      \"evidence\": \"Co-IP with Snail1 and functional EMT assays in ovarian cancer; Twist epistasis in DOX-resistant HCC; kinase inhibitor/GSK-3\\u03b2 knockdown in RCC with xenografts\",\n      \"pmids\": [\"30231243\", \"29568938\", \"29148041\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of Snail1 stabilization by FSCN1 not defined\", \"Direct vs indirect kinase regulation not resolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Defined the GRHL3\\u2192FSCN1\\u2192E-cadherin axis in collective epithelial migration, extending FSCN1 function beyond cancer to physiological wound healing.\",\n      \"evidence\": \"ATAC-seq for GRHL3-motif accessibility, Grhl3 conditional knockout mice, wound-healing and E-cadherin analysis\",\n      \"pmids\": [\"34494554\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct GRHL3 binding to FSCN1 locus not shown by ChIP\", \"How FSCN1 mechanistically relaxes adherens junctions unclear\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Mapped the FSCN1 protein interactome, nominating filopodium-assembly, GTPase, adhesion, and metabolic partners as candidate effectors.\",\n      \"evidence\": \"Co-IP/mass spectrometry in laryngeal carcinoma cell lines with western/IF validation of AIMP1 and LTA4H\",\n      \"pmids\": [\"31287215\", \"31298480\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequences of individual interactions not reconstituted\", \"Interactome from single cancer type\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Added a transcriptional and mRNA-stability layer to FSCN1 control via the nucleolar factor LYAR and the lncRNA/HuR axis, linking FSCN1 to fatty acid synthesis and AKT activation.\",\n      \"evidence\": \"ChIP/reporter assays for LYAR in colorectal cancer; RNA pull-down/RIP/stability assays for ADORA2A-AS1\\u2013HuR\\u2013FSCN1 in HCC with xenografts\",\n      \"pmids\": [\"35069968\", \"34733789\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism linking FSCN1 to FASN/SCD not defined\", \"Single-lab findings per axis\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extended FSCN1 signaling to the tumor microenvironment, showing it binds IGF-1R to drive PI3K-AKT/JAK-STAT activation and macrophage M2 polarization.\",\n      \"evidence\": \"Co-IP, Seahorse metabolic analysis, cytokine qRT-PCR, and in vivo imaging in lung adenocarcinoma\",\n      \"pmids\": [\"36223033\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single Co-IP without reciprocal validation\", \"Direct vs adaptor role of FSCN1 at IGF-1R unclear\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identified a non-canonical RNA-binding function and protein-level stabilizers, broadening FSCN1's mechanism beyond cytoskeletal bundling.\",\n      \"evidence\": \"RIP showing FSCN1 binding to PTK6 pre-mRNA in esophageal cancer; Co-IP/stability assays for SYTL2 and NQO1 with in vivo rescue in prostate and arsenic-transformed lung cells\",\n      \"pmids\": [\"35401239\", \"37147713\", \"37424815\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"RNA-binding domain/motif of FSCN1 not mapped\", \"How SYTL2/NQO1 block FSCN1 ubiquitination not defined\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Validated FSCN1 as a pharmacological target downstream of \\u03b2-catenin, with small-molecule inhibition collapsing cytoskeletal structures and suppressing invasion and pathological angiogenesis.\",\n      \"evidence\": \"CRISPR KO plus G2-044 inhibitor and zebrafish metastasis model; NP-G2-044 in endothelial assays and OIR/CNV mouse models\",\n      \"pmids\": [\"36971100\", \"37596693\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Inhibitor selectivity over fascin paralogs not addressed in timeline\", \"Angiogenesis interaction partners not fully defined\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Connected acetylation-controlled splicing to Fscn1 expression, showing a p300\\u2192SF3A2(K10)\\u2192Fscn1 splicing axis with a cardioprotective, mitochondrial-respiration outcome.\",\n      \"evidence\": \"Acetylomic proteomics, SPR/CETSA binding kinetics, site-specific mutagenesis, and Seahorse in cardiomyocytes treated with ginsenoside Rb2\",\n      \"pmids\": [\"38101749\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Which Fscn1 isoform mediates mitochondrial protection not specified\", \"Direct role of FSCN1 protein in respiration mechanism unresolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established m6A-dependent stabilization of FSCN1 mRNA by viral oncogenes, adding epitranscriptomic regulation to its control.\",\n      \"evidence\": \"HPV16 E6/E7 and METTL14/IGF2BP3 knockdown with rescue in cervical carcinoma cells\",\n      \"pmids\": [\"38679464\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"m6A site on FSCN1 mRNA not mapped\", \"Single-lab study\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrated an epigenetic-neuronal role: KDM7A demethylation activates Fscn1 to support dendritic spine density and drug-reward memory, extending FSCN1 function into CNS plasticity.\",\n      \"evidence\": \"Locus-specific H3K9me2/H3K27me2 ChIP, viral Fscn1 knockdown, spine morphology, and conditioned place preference behavior in mPFC neurons\",\n      \"pmids\": [\"39836528\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How actin-bundling drives spine density mechanistically not dissected\", \"KDM7A binding to Fscn1 promoter inferred from demethylation only\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How FSCN1's distinct activities — actin bundling, receptor trafficking, RNA binding, and partner-controlled stability — are coordinated within a single cell and whether they share a common structural determinant remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model integrating actin-bundling and RNA-binding functions\", \"Regulatory hierarchy among transcriptional, m6A, miRNA, and protein-stability controls not established\", \"Tissue-specific selection among FSCN1's functions unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 14, 15]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [11]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [14, 15]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 10, 18]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [1, 20]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [14, 17]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TGFBR1\", \"SNAI1\", \"IGF1R\", \"SYTL2\", \"NQO1\", \"AIMP1\", \"LTA4H\", \"HuR\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}