Affinage

ECM1

Extracellular matrix protein 1 · UniProt Q16610

Length
540 aa
Mass
60.7 kDa
Annotated
2026-06-09
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ECM1 is a secreted glycoprotein that functions as a multivalent extracellular scaffold and signaling modulator, organizing basement membrane architecture while restraining latent TGF-β1 activation across multiple tissues (PMID:31362006, PMID:39448254). As a structural organizer it binds perlecan domain V through its C-terminus (PMID:12604605) and engages laminin 332, collagen IV, fibronectin, fibulin-3, and glycosaminoglycans through distinct domains, enhancing collagen IV–laminin 332 association within the skin basement membrane (PMID:18200062, PMID:19275936). In the liver, hepatocyte- and hepatic stellate cell–derived ECM1 maintains TGF-β1 in its inactive latent state by binding αv integrins and by directly interacting with the TGF-β1 activators TSP-1 and ADAMTS1 (via their KRFK/KTFR sequences) while suppressing MMP-2/9 activity, thereby enforcing stellate cell quiescence; its loss precipitates spontaneous, fatal liver fibrosis (PMID:31362006, PMID:39448254, PMID:41854361). ECM1 further protects hepatocytes by engaging the iron chaperone PCBP1 to limit iron overload and lipid peroxidation (PMID:40372944) and the cystine/glutamate transporter xCT (SLC7A11) to restrain ferroptosis (PMID:38184998), and signals through the surface receptor LRP1α to suppress AKT/mTOR and activate FoxO1 (PMID:40336034). In immunity, ECM1 binds the IL-2 receptor on TH2 cells to inhibit IL-2 signaling and restore KLF2/S1P1-driven lymph node egress (PMID:21217760), and drives LPS-induced M1 macrophage polarization via GM-CSF/STAT5 signaling (PMID:31980528). In cancer, ECM1 promotes invasion and EMT through MUC1-dependent β-catenin stabilization (PMID:25746001), EGF/ERK-driven PKM2(Ser37) phosphorylation and Warburg metabolism (PMID:25446258), and ENO1(Y189)/GRB2/SOS1/MAPK signaling (PMID:39563492). ECM1 transcription is activated by TFAP2C (PMID:24023917) and by EGF/EGFR–STAT1(S727) signaling, and repressed during inflammation by IFNγ-induced STAT1(Y701) and NRF2 (PMID:40671832). Loss-of-function affecting ECM1 secretion underlies lipoid proteinosis, reflecting failure of basement membrane scaffolding (PMID:25379385).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2001 Medium

    Established that ECM1 is not merely a structural component but has direct biological activity, showing it stimulates endothelial proliferation and angiogenesis.

    Evidence Recombinant ECM1 in endothelial proliferation and chick chorioallantoic membrane assays

    PMID:11292659

    Open questions at the time
    • No receptor or signaling pathway for the angiogenic effect identified
    • Single lab, in vitro/CAM only
  2. 2003 High

    Identified the first physical partner of ECM1, defining a molecular basis for its incorporation into the basement membrane network.

    Evidence Yeast two-hybrid plus reciprocal Co-IP and deletion mapping of ECM1 C-terminus–perlecan domain V interaction

    PMID:12604605

    Open questions at the time
    • Functional consequence of perlecan binding in vivo not established
    • No structural model of the interface
  3. 2008 Medium

    Demonstrated ECM1 acts as a multivalent matrix cross-linker, mapping its binding to several ECM components and placing it ultrastructurally in the skin basement membrane.

    Evidence Solid-phase binding assays, immunoelectron microscopy, immunohistochemistry

    PMID:18200062

    Open questions at the time
    • Binding affinities not quantified
    • Causal role of cross-linking in basement membrane integrity not tested by mutation
  4. 2009 High

    Mapped a specific ECM1 domain (SASDL2) to fibulin-3 and laminin 332 β3 binding, refining the structural logic of its scaffolding function.

    Evidence Yeast two-hybrid, in vitro/in vivo Co-IP, domain mapping, immunohistochemistry

    PMID:19275936

    Open questions at the time
    • Effect of disrupting SASDL2 binding on tissue phenotype not shown
  5. 2011 High

    Revealed an unexpected immunological role, showing ECM1 controls TH2 cell lymph node egress by binding the IL-2 receptor and modulating KLF2/S1P1.

    Evidence ECM1-knockout mice, in vivo TH2 assays, direct IL-2 receptor binding, flow cytometry

    PMID:21217760

    Open questions at the time
    • Stoichiometry and structural basis of IL-2 receptor binding undefined
    • Whether secreted vs cell-associated ECM1 mediates this is unclear
  6. 2014 Medium

    Connected ECM1 to cancer metabolism and post-translational regulation, linking it to PKM2(Ser37) phosphorylation/Warburg effect and identifying N-glycosylation sites that govern its secretion.

    Evidence Proteomics and Western blot for PKM2 phosphorylation; mass spectrometry glycosite mapping and secretion mutagenesis

    PMID:25379385 PMID:25446258

    Open questions at the time
    • Direct ECM1–EGF/EGFR engagement not reconstituted
    • Glycosylation findings do not explain LP-mutation secretion defects
  7. 2015 Medium

    Defined a mechanism for ECM1-driven metastasis through MUC1-dependent post-translational β-catenin stabilization and EMT.

    Evidence ECM1 KD/OE, MUC1–β-catenin Co-IP, sphere-forming and invasion assays in breast cancer

    PMID:25746001

    Open questions at the time
    • How extracellular ECM1 signals to intracellular MUC1/β-catenin not established
    • Single lab
  8. 2013 High

    Established the transcriptional control of ECM1, defining its minimal promoter elements and identifying TFAP2C as a direct activator in melanoma.

    Evidence Promoter deletion/point mutagenesis CAT and luciferase reporters; ChIP-seq, EMSA, KD/OE for TFAP2C

    PMID:24023917 PMID:9931498

    Open questions at the time
    • Upstream signals converging on AP1/Sp1/Ets in non-cancer tissues not mapped
  9. 2013 Medium

    Showed a developmental patterning role, with stromal ECM1 restricting Ret expression and ureteric bud branching during kidney development downstream of retinoic acid.

    Evidence In vivo Ecm1 inhibition, immunofluorescence, Ret expression analysis

    PMID:24391906

    Open questions at the time
    • Receptor mediating ECM1 action on ureteric bud unknown
    • Single model system
  10. 2016 Medium

    Linked ECM1 to cytoskeletal regulation in cancer cells via an S100A4/RhoA axis controlling actin dynamics and migration.

    Evidence siRNA KD, RhoA pull-down, F/G actin ratio, S100A4 rescue in breast cancer cells

    PMID:27770373

    Open questions at the time
    • Mechanism connecting secreted ECM1 to intracellular S100A4/RhoA not defined
  11. 2019 High

    Identified the central antifibrotic mechanism of ECM1 in liver: maintaining latent TGF-β1 inactive via αv integrin interaction to keep hepatic stellate cells quiescent.

    Evidence Global and hepatocyte-specific ECM1-KO mice, AAV rescue, soluble TGFBR2 rescue, CCl4 model

    PMID:31362006

    Open questions at the time
    • Structural basis of ECM1–αv integrin binding not resolved
    • Cross-tissue generality of TGF-β1 control not addressed here
  12. 2020 High

    Extended ECM1's immune role to innate immunity, showing it drives M1 macrophage polarization through GM-CSF/STAT5 with relevance to IBD; in parallel established its role in tumor angiogenic crosstalk via NOTCH.

    Evidence Macrophage-specific KO, DSS colitis model, STAT5 analysis; secretome MS, CRISPRi/CRISPRa, recombinant ECM1 in endothelial co-culture

    PMID:31980528 PMID:32203150

    Open questions at the time
    • Receptor coupling ECM1 to GM-CSF/STAT5 in macrophages not identified
    • NOTCH induction mechanism by ECM1 indirect
  13. 2024 High

    Resolved the mechanistic detail of TGF-β1 restraint and uncovered new hepatocyte-protective interactions, showing ECM1 binds TSP-1/ADAMTS1 (KRFK/KTFR) and MMP-2/9 to block activation, binds PCBP1 to limit iron-driven lipid peroxidation, and binds xCT to restrain ferroptosis.

    Evidence In vitro interaction/peptide assays and KO mice (TGF-β1); Co-IP and KO/OE MASH models (PCBP1); ECM1–xCT interaction and hepatocyte KO (ferroptosis)

    PMID:38184998 PMID:39448254 PMID:40372944

    Open questions at the time
    • Whether one ECM1 molecule coordinates multiple partners simultaneously unknown
    • Stoichiometry of xCT and PCBP1 binding undefined
  14. 2024 Medium

    Identified additional surface-receptor signaling axes for ECM1 in cancer (ENO1/MAPK driving anti-androgen resistance) and a transcriptional/degradation control layer (NF-κB induction, TET2 demethylation, celastrol-induced ubiquitination).

    Evidence Co-IP and phospho-ENO1(Y189) assays in prostate cancer; promoter/NF-κB and TET2 methylation analyses; docking/CESTA/ubiquitination assays

    PMID:36145166 PMID:38172938 PMID:39494325 PMID:39563492

    Open questions at the time
    • Direct ECM1–ENO1 binding interface not structurally defined
    • Generality of NF-κB and TET2 regulation across tissues untested
  15. 2025 High

    Completed the liver regulatory circuit by defining how ECM1 transcription is sustained and suppressed (EGF/EGFR–STAT1-S727 activating; IFNγ–STAT1-Y701/NRF2 repressing) and identified LRP1α as a receptor mediating antifibrotic AKT/mTOR-FoxO1 signaling.

    Evidence Phospho-specific STAT1 mutants, ChIP, multiple CLD mouse models; Co-IP/PLA/pull-down and LRP1-deficient mice

    PMID:40336034 PMID:40671832

    Open questions at the time
    • How ECM1 selects among LRP1, αv integrin, and other receptors in a given context unclear
    • Interplay between transcriptional repression and protein-level regulation not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single secreted ECM1 protein selects among its many partners and surface receptors (integrins, IL-2R, LRP1, ENO1, xCT, PCBP1) to produce context-specific outcomes, and whether a common structural/biochemical logic governs these engagements.
  • No integrated structural model of ECM1's multivalent binding
  • Receptor selection rules across cell types unknown
  • Quantitative affinities and competition among partners undetermined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0005198 structural molecule activity 2
Localization
GO:0005576 extracellular region 3 GO:0031012 extracellular matrix 3
Pathway
GO:0140110 transcription regulator activity 3 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 2
Partners
FBLN3HSPG2ITGAVLAMB3LRP1PCBP1SLC7A11THBS1

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 ECM1 physically interacts with perlecan domain V; specifically, the C-terminus of ECM1 binds the EGF-like modules flanking the LG2 subdomain of perlecan domain V. This was identified by yeast two-hybrid screening of a human keratinocyte cDNA library and validated by co-immunoprecipitation in cell-free systems and mammalian cells using deletion mutants to map the binding sites. Yeast two-hybrid, co-immunoprecipitation (cell-free and mammalian cells), deletion mutant mapping The Journal of biological chemistry High 12604605
2001 Recombinant ECM1 protein stimulates proliferation of cultured endothelial cells and promotes blood vessel formation in the chick chorioallantoic membrane assay, establishing direct pro-angiogenic activity. Endothelial cell proliferation assay with purified recombinant ECM1; chorioallantoic membrane (CAM) angiogenesis assay FASEB journal Medium 11292659
2008 ECM1a binds multiple extracellular matrix components including laminin 332, collagen type IV, fibronectin, hyaluronan, heparin, and chondroitin sulfate A via distinct regions of the protein, as shown by solid-phase binding assays. ECM1a enhances collagen IV binding to laminin 332 in a dose-dependent manner. Ultrastructural analysis placed ECM1 at the skin basement membrane within a network containing perlecan, collagen IV, and laminin 332. Solid-phase binding assay, immunoelectron microscopy, immunohistochemistry The Journal of investigative dermatology Medium 18200062
2009 ECM1a binds fibulin-3 and the beta-3 chain of laminin 332 through its serum albumin subdomain-like 2 (SASDL2) domain, as established by yeast two-hybrid screening and confirmed by in vitro and in vivo co-immunoprecipitation. Both partners co-localize with ECM1 in human skin by immunohistochemistry. Yeast two-hybrid, in vitro co-immunoprecipitation, in vivo co-immunoprecipitation, immunohistochemistry Matrix biology High 19275936
2011 ECM1 is selectively expressed in TH2 cells and controls their egress from lymph nodes by directly binding the IL-2 receptor to inhibit IL-2 signaling, which in turn promotes re-expression of KLF2 and S1P1. ECM1-deficient T cells showed impaired migration and retention in lymphoid organs despite normal TH2 polarization. ECM1-knockout mouse model; in vivo TH2 response assays; direct IL-2 receptor binding experiment; flow cytometry; gene expression analysis Nature immunology High 21217760
2019 ECM1 (produced mainly by hepatocytes) stabilizes extracellular matrix-deposited TGF-β1 in its inactive (latent) form by interacting with αv integrins, thereby preventing hepatic stellate cell (HSC) activation and fibrogenesis. ECM1-knockout mice spontaneously develop fatal liver fibrosis without significant hepatocyte damage. Ectopic expression of ECM1 or soluble TGFBR2 prevented fibrogenesis in ECM1-KO mice. ECM1-KO and hepatocyte-specific KO mice; AAV-mediated ECM1 overexpression; co-culture assays; immunohistochemistry; CCl4 fibrosis model; reporter gene assays Gastroenterology High 31362006
2020 ECM1 in macrophages promotes M1 polarization in response to LPS through the GM-CSF/STAT5 signaling pathway. Macrophage-specific ECM1 knockout increased ARG1 expression and impaired M1 polarization, and alleviated DSS-induced IBD pathology in mice. Macrophage-specific ECM1 knockout mice; LPS stimulation; STAT5 pathway analysis; DSS-induced colitis model; cytokine measurement PNAS High 31980528
2015 ECM1 stabilizes β-catenin expression at the post-translational level through induction of MUC1, which physically associates with β-catenin. This β-catenin stabilization drives EMT progression and cancer stem cell maintenance, promoting breast cancer metastasis. ECM1 knockdown/overexpression; co-immunoprecipitation of MUC1–β-catenin complex; Western blot; sphere-forming assay; migration/invasion assay Oncogene Medium 25746001
2014 ECM1 promotes the Warburg effect in cancer cells by inducing EGF-dependent ERK activation, which phosphorylates PKM2 at Ser37, leading to upregulation of GLUT1, LDHA, and HIF-1α gene expression. 2D-LC-MS/MS proteomics; Western blot for PKM2 phosphorylation; gene expression analysis; ECM1 overexpression/knockdown Cellular signalling Medium 25446258
2013 In kidney development, ECM1 is secreted from cortical stromal cells and acts on the ureteric bud to restrict Ret expression to the tips; inhibition of Ecm1 results in an expanded domain of Ret expression and reduced ureteric bud branching. Ecm1 was identified as a retinoic acid-regulated target in stromal cells. In vivo kidney development studies; Ecm1 inhibition; immunofluorescence; Ret expression analysis; retinoic acid signaling studies PloS one Medium 24391906
2014 N-glycosylation of ECM1 at Asn354 negatively regulates its secretion; this site (and Asn444) were identified as actual N-glycosylation sites by mass spectrometry. LP-associated ECM1 mutations suppress ECM1 secretion, but this suppression is not caused by loss of N-glycosylation at these sites. Mass spectrometry identification of glycosylation sites; mutagenesis of N-glycosylation sites; secretion assay FEBS open bio Medium 25379385
1999 The Ecm1 promoter requires AP1, Sp1, and Ets binding sites for expression in osteogenic cells; a 110-bp fragment containing these sites is sufficient for promoter activity. Point mutation analysis showed that all three sites are absolutely necessary. A repressive region was identified between −110 and −317. Reporter gene (CAT) assays; progressive promoter deletion; point mutagenesis; transient transfection in MN7 cells Gene Medium 9931498
2016 ECM1 regulates the actin cytoskeletal architecture of breast cancer cells partly via S100A4 and RhoA GTPase. ECM1 silencing decreased S100A4 and TGFβR2 expression, increased F/G actin ratio, induced stress fiber formation, reduced RhoA activation, and impaired cell migration and invasion. Re-expression of S100A4 rescued the phenotype in Hs578T cells. siRNA knockdown; activated Rho GTPase pull-down assay; F/G actin ratio measurement; fluorescent actin staining; migration/invasion assays; rescue experiment Clinical & experimental metastasis Medium 27770373
2013 TFAP2C directly binds the ECM1 promoter at an AP2 regulatory region and transcriptionally activates ECM1 expression in melanoma cells. TFAP2C knockdown reduced ECM1 expression; TFAP2C overexpression increased it. The minimal promoter (∼100 bp) containing AP1, SP1, Ets, and TATA box binding sites was sufficient for promoter activity. siRNA knockdown; adenoviral overexpression; luciferase reporter assays; 5' RACE; ChIP-seq for TFAP2C; gel shift assay (EMSA) PloS one High 24023917
2020 ECM1 secreted by HER2-overexpressing breast cancer cells induces NOTCH1 and NOTCH3 upregulation in endothelial cells, promoting endothelial network formation and an endothelial feedback that enhances cancer cell migration and invasion. ECM1 knockdown by CRISPRi abolished these effects; recombinant ECM1 recapitulated them. Secretome MS; CRISPRi/CRISPRa knockdown/overexpression; conditioned medium experiments; recombinant ECM1 treatment; NOTCH inhibitor studies; 2D/3D co-culture Laboratory investigation Medium 32203150
2024 ECM1 inhibits latent TGF-β1 activation by directly interacting with TSP-1 and ADAMTS1 via their KRFK or KTFR amino acid sequences, and by suppressing MMP-2/9 proteolytic activity. In vitro interaction assays confirmed these direct protein-protein interactions; ECM1 overexpression in mice attenuated KRFK-induced LTGF-β1 activation. In vitro interaction assays; HSC overexpression; Ecm1-KO and Fxr-KO mice; RNAseq; KTFR peptide treatment; computer modeling Gut High 39448254
2024 ECM1 interacts with the K-homology 3 (KH3) domain of PCBP1 to suppress intracellular iron overload, thereby limiting lipid peroxidation and MASH progression. ECM1 overexpression blocked hepatic steatosis and inflammation; ECM1 ablation exacerbated MASH. Re-expression of both ECM1 and PCBP1 ameliorated liver disease. Co-immunoprecipitation (ECM1–PCBP1 interaction); hepatocyte-specific ECM1 KO; AAV-mediated ECM1 overexpression; multiple MASH mouse models; iron and lipid peroxidation assays Hepatology High 40372944
2024 ECM1 interacts with the cell-surface receptor enolase 1 (ENO1) on prostate cancer cells, leading to ENO1 phosphorylation at Y189, which recruits GRB2 and SOS1 adapter proteins and activates the MAPK signaling pathway, thereby promoting anti-androgen resistance in bone metastatic prostate cancer. Co-immunoprecipitation; phosphorylation assays; ENO1 inhibitor (PhAH); ENO1/ECM1 knockdown; MAPK pathway analysis Advanced science Medium 39563492
2025 ECM1 directly binds the cell-surface receptor LRP1α (low-density lipoprotein receptor-related protein 1α) as confirmed by Co-IP, Duolink Proximity Ligation Assay, and pull-down assays. The ECM1–LRP1 axis attenuates liver fibrosis by suppressing AKT/mTOR while activating the FoxO1 signaling pathway. LRP1-deficient mice lost the antifibrotic effect of ECM1-modified MenSCs. Co-immunoprecipitation, proximity ligation assay, pull-down; LRP1-deficient mice (AAV8-mediated); non-target metabolomics; RNA-seq Stem cell research & therapy High 40336034
2025 In healthy hepatocytes, EGF/EGFR signaling sustains ECM1 expression by phosphorylating STAT1 at Ser727, enhancing its binding to the ECM1 promoter. During liver inflammation, IFNγ inhibits this mechanism by phosphorylating STAT1 at Tyr701 (impairing pSTAT1-S727 promoter binding) and induces NRF2 nuclear translocation, which repressively binds the ECM1 promoter, together reducing ECM1 transcription. Promoter analysis; STAT1 phospho-mutant assays; ChIP; functional assays in AML12 cells and primary hepatocytes; multiple CLD mouse models; scRNA-seq; AAV8-ECM1 rescue JHEP reports High 40671832
2022 ECM1 gene transcription is regulated by NF-κB through EP881C/T-EP266C binding sites in its promoter. Cisplatin activates NF-κB phosphorylation to enhance ECM1 expression, and the IKK/IκB/NF-κB pathway governs ECM1 levels. Secreted ECM1 can activate normal fibroblasts to acquire cancer-associated fibroblast characteristics. Promoter analysis; NF-κB inhibition (WA compound targeting IKK/IκB); Western blot for phospho-NF-κB; ECM1 overexpression; fibroblast co-culture Nutrients Medium 36145166
2024 ECM1 interacts with the cystine/glutamate transporter xCT (SLC7A11) to regulate hepatocyte ferroptosis. ECM1 deletion in hepatocytes abolished the antifibrotic effect of Sal B and exacerbated ferroptosis. Sal B upregulates ECM1 expression and directly binds ECM1 (binding kinetics determined). Co-interaction assay (ECM1–xCT); Ecm1 hepatocyte-specific KO mice; in vitro ferroptosis models; binding kinetics assay Redox biology Medium 38184998
2024 TET2-mediated demethylation of the ECM1 promoter upregulates ECM1 expression in high-glucose-treated retinal microvascular endothelial cells. TET2 knockdown decreased both ECM1 expression and promoter methylation reversion, reducing tube formation and migration, implicating ECM1 as a downstream effector of TET2-driven neovascularization in diabetic retinopathy. TET2 knockdown; ECM1 promoter methylation analysis; tube formation and migration assays in HRMECs; gene expression datasets Clinical epigenetics Medium 38172938
2024 Celastrol directly binds ECM1 and promotes its ubiquitination and proteasomal degradation, thereby inhibiting M1-like macrophage polarization and the ECM1/STAT5 pathway in IgA nephropathy. Confirmed by molecular docking, cellular thermal shift assay (CESTA), and co-immunoprecipitation. Molecular docking; CESTA (cellular thermal shift assay); co-immunoprecipitation; ubiquitination assay; macrophage polarization assay; IgAN mouse model International journal of biological sciences Medium 39494325
2019 ECM1 stimulation of cardiac fibroblasts induces ERK1/2 and AKT activation and upregulates collagen-I expression in vitro, suggesting a pro-fibrotic signaling role. ECM1 is expressed by bone marrow-derived granulocytes rather than resident cardiac cells, and is expressed at the infarct zone at day 3 post-MI. Recombinant ECM1 treatment of cardiac fibroblasts; Western blot for pERK1/2, pAKT; collagen-I qPCR; mRNA-FISH; flow cytometry of bone marrow PloS one Medium 30789914
2026 In the MASH disease context, ECM1 produced by hepatic stellate cells enforces HSC quiescence. HSC-specific ECM1 overexpression suppressed CCl4-induced fibrosis. ECM1 expression in quiescent HSCs inversely correlated with fibrosis stage in human biopsies across multiple CLD etiologies. HSC-specific ablation (Lrat-iDTR mice); HSC-specific ECM1 overexpression; RNA-seq; multi-parametric analysis; human biopsy correlation Hepatology Medium 41854361

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Lipoid proteinosis maps to 1q21 and is caused by mutations in the extracellular matrix protein 1 gene (ECM1). Human molecular genetics 205 11929856
2003 Perlecan protein core interacts with extracellular matrix protein 1 (ECM1), a glycoprotein involved in bone formation and angiogenesis. The Journal of biological chemistry 152 12604605
2001 Extracellular matrix protein 1 (ECM1) has angiogenic properties and is expressed by breast tumor cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 121 11292659
2013 Differential diagnosis of azoospermia with proteomic biomarkers ECM1 and TEX101 quantified in seminal plasma. Science translational medicine 120 24259048
2020 ECM1 is an essential factor for the determination of M1 macrophage polarization in IBD in response to LPS stimulation. Proceedings of the National Academy of Sciences of the United States of America 116 31980528
2019 ECM1 Prevents Activation of Transforming Growth Factor β, Hepatic Stellate Cells, and Fibrogenesis in Mice. Gastroenterology 110 31362006
2003 Extracellular matrix protein 1 gene (ECM1) mutations in lipoid proteinosis and genotype-phenotype correlation. The Journal of investigative dermatology 106 12603844
2005 ECM1 and TMPRSS4 are diagnostic markers of malignant thyroid neoplasms and improve the accuracy of fine needle aspiration biopsy. Annals of surgery 102 16135921
2003 Extracellular matrix protein 1 (ECM1) is over-expressed in malignant epithelial tumors. Cancer letters 99 14550953
2015 ECM1 regulates tumor metastasis and CSC-like property through stabilization of β-catenin. Oncogene 88 25746001
1997 The human extracellular matrix gene 1 (ECM1): genomic structure, cDNA cloning, expression pattern, and chromosomal localization. Genomics 79 9367673
2024 Salvianolic acid B attenuates liver fibrosis by targeting Ecm1 and inhibiting hepatocyte ferroptosis. Redox biology 70 38184998
2016 MiR-486-3p targeting ECM1 represses cell proliferation and metastasis in cervical cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 58 27133046
2008 Interaction of extracellular matrix protein 1 with extracellular matrix components: ECM1 is a basement membrane protein of the skin. The Journal of investigative dermatology 58 18200062
2011 ECM1 controls T(H)2 cell egress from lymph nodes through re-expression of S1P(1). Nature immunology 54 21217760
2020 miR-193a-5p promotes pancreatic cancer cell metastasis through SRSF6-mediated alternative splicing of OGDHL and ECM1. American journal of cancer research 53 32064152
2018 Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1. Oncogene 52 29858602
2014 Integrated analyses of DNA methylation and hydroxymethylation reveal tumor suppressive roles of ECM1, ATF5, and EOMES in human hepatocellular carcinoma. Genome biology 49 25517360
2016 Extracellular matrix 1 (ECM1) regulates the actin cytoskeletal architecture of aggressive breast cancer cells in part via S100A4 and Rho-family GTPases. Clinical & experimental metastasis 43 27770373
2009 ECM1 interacts with fibulin-3 and the beta 3 chain of laminin 332 through its serum albumin subdomain-like 2 domain. Matrix biology : journal of the International Society for Matrix Biology 41 19275936
2014 ECM1 promotes the Warburg effect through EGF-mediated activation of PKM2. Cellular signalling 39 25446258
2025 ECM1 attenuates hepatic fibrosis by interfering with mediators of latent TGF-β1 activation. Gut 38 39448254
2020 ECM1 secreted by HER2-overexpressing breast cancer cells promotes formation of a vascular niche accelerating cancer cell migration and invasion. Laboratory investigation; a journal of technical methods and pathology 35 32203150
2019 Novel role of extracellular matrix protein 1 (ECM1) in cardiac aging and myocardial infarction. PloS one 34 30789914
2012 Overexpression of ECM1 contributes to migration and invasion in cholangiocarcinoma cell. Neoplasma 34 22489696
2016 ECM1 promotes migration and invasion of hepatocellular carcinoma by inducing epithelial-mesenchymal transition. World journal of surgical oncology 33 27460906
2019 Extracellular matrix protein 1 (ECM1) is associated with carcinogenesis potential of human bladder cancer. OncoTargets and therapy 31 30863109
2019 Long noncoding RNA FALEC inhibits proliferation and metastasis of tongue squamous cell carcinoma by epigenetically silencing ECM1 through EZH2. Aging 30 31335317
2022 ECM1 modified HF-MSCs targeting HSC attenuate liver cirrhosis by inhibiting the TGF-β/Smad signaling pathway. Cell death discovery 26 35136027
2013 Stromal protein Ecm1 regulates ureteric bud patterning and branching. PloS one 26 24391906
2022 The Effect of Shionone on Sepsis-Induced Acute Lung Injury by the ECM1/STAT5/NF-κB Pathway. Frontiers in pharmacology 25 35153740
2006 Expression of extracellular matrix protein 1 (ECM1) in human skin is decreased by age and increased upon ultraviolet exposure. The British journal of dermatology 24 16433788
2024 Paris saponin VII reverses resistance to PARP inhibitors by regulating ovarian cancer tumor angiogenesis and glycolysis through the RORα/ECM1/VEGFR2 signaling axis. International journal of biological sciences 21 38725854
2022 ECM1 regulates the resistance of colorectal cancer to 5-FU treatment by modulating apoptotic cell death and epithelial-mesenchymal transition induction. Frontiers in pharmacology 21 36408224
2021 HLA-A2.1-restricted ECM1-derived epitope LA through DC cross-activation priming CD8+ T and NK cells: a novel therapeutic tumour vaccine. Journal of hematology & oncology 21 33910591
2018 Proteomic Analysis of Liquid Biopsy from Tumor-Draining Vein Indicates that High Expression of Exosomal ECM1 Is Associated with Relapse in Stage I-III Colon Cancer. Translational oncology 21 29660691
2022 Shionone Attenuates Sepsis-Induced Acute Kidney Injury by Regulating Macrophage Polarization via the ECM1/STAT5 Pathway. Frontiers in medicine 20 35141243
2019 Downregulation of Long Non-coding RNA FALEC Inhibits Gastric Cancer Cell Migration and Invasion Through Impairing ECM1 Expression by Exerting Its Enhancer-Like Function. Frontiers in genetics 20 30984243
2013 Human Melanoma cells over-express extracellular matrix 1 (ECM1) which is regulated by TFAP2C. PloS one 20 24023917
2021 Brusatol Inhibits Proliferation and Invasion of Glioblastoma by Down-Regulating the Expression of ECM1. Frontiers in pharmacology 19 34970146
2019 miR-23a-5p inhibits cell proliferation and invasion in pancreatic ductal adenocarcinoma by suppressing ECM1 expression. American journal of translational research 19 31217868
2023 Urinary Eubacterium sp. CAG:581 Promotes Non-Muscle Invasive Bladder Cancer (NMIBC) Development through the ECM1/MMP9 Pathway. Cancers 18 36765767
2023 Citri Reticulatae Pericarpium-Reynoutria japonica Houtt. herb pair suppresses breast cancer liver metastasis by targeting ECM1-mediated cholesterol biosynthesis pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 17 37247588
2022 Wentilactone A Reverses the NF-κB/ECM1 Signaling-Induced Cisplatin Resistance through Inhibition of IKK/IκB in Ovarian Cancer Cells. Nutrients 16 36145166
2020 MiR-486-3p inhibits the proliferation, migration and invasion of retinoblastoma cells by targeting ECM1. Bioscience reports 16 32401301
2015 Lipoid proteinosis: phenotypic heterogeneity in Iranian families with c.507delT mutation in ECM1. Experimental dermatology 15 25529926
2005 A novel splice-site mutation in ECM-1 gene in a consanguineous family with lipoid proteinosis. Experimental dermatology 15 16274456
2024 TET2-mediated ECM1 hypomethylation promotes the neovascularization in active proliferative diabetic retinopathy. Clinical epigenetics 13 38172938
2014 Treatment of lipoid proteinosis due to the p.C220G mutation in ECM1, a major allele in Chinese patients. Journal of translational medicine 13 24708644
2011 Molecular analysis of lipoid proteinosis: identification of a novel nonsense mutation in the ECM1 gene in a Pakistani family. Diagnostic pathology 13 21791056
2005 A novel mutation of the extracellular matrix protein 1 gene (ECM1) in a patient with lipoid proteinosis (Urbach-Wiethe disease) from Sicily. The British journal of dermatology 13 16225617
2019 ATG16L1 T300A polymorphism is associated with Crohn's disease in a Northwest Greek cohort, but ECM1 T130M and G290S polymorphisms are not associated with ulcerative colitis. Annals of gastroenterology 12 31892796
1999 Molecular cloning and characterization of the mouse Ecm1 gene and its 5' regulatory sequences. Gene 12 9931498
2024 ECM1 and KRT6A are involved in tumor progression and chemoresistance in the effect of dexamethasone on pancreatic cancer. Cancer science 11 38613239
2016 eQTL analysis links inflammatory bowel disease associated 1q21 locus to ECM1 gene. Journal of applied genetics 11 26738999
2014 N-Glycosylation of extracellular matrix protein 1 (ECM1) regulates its secretion, which is unrelated to lipoid proteinosis. FEBS open bio 11 25379385
2007 Homozygous missense mutation in the ECM1 gene in Chinese siblings with lipoid proteinosis. Acta dermato-venereologica 11 17721643
2007 ECM1 expression in thyroid tumors--a comparison of real-time RT-PCR and IHC. The Journal of surgical research 11 18374945
2024 ECM1 and ANXA1 in urinary extracellular vesicles serve as biomarkers for breast cancer. Frontiers in oncology 10 39040439
2024 Mechanistic study of celastrol-mediated inhibition of proinflammatory activation of macrophages in IgA nephropathy via down-regulating ECM1. International journal of biological sciences 10 39494325
2016 A Novel ECM1 Splice Site Mutation in Lipoid Proteinosis: Case Report plus Review of the Literature. Molecular syndromology 9 27194970
2012 A novel missense mutation of the ECM1 gene in a Chinese patient with lipoid proteinosis. Clinical and experimental dermatology 9 22182433
2021 Light-control of cap methylation and mRNA translation via genetic code expansion of Ecm1. Chemical science 8 34163701
2025 ECM1 protects against liver steatosis through PCBP1-mediated iron homeostasis. Hepatology (Baltimore, Md.) 7 40372944
2024 Osteoblast-Derived ECM1 Promotes Anti-Androgen Resistance in Bone Metastatic Prostate Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 7 39563492
2017 The Characteristics and Long-Term Course of Epilepsy in Lipoid Proteinosis: A Spectrum From Mild to Severe Seizures in Relation to ECM1 Mutations. Clinical EEG and neuroscience 7 28434238
2022 ECM1 is associated with endocrine resistance in ER+ breast cancers. Animal cells and systems 6 35784388
2024 A founder deletion in ECM1 of 1163 bp causes lipoid proteinosis in the southeast region of Turkiye. American journal of medical genetics. Part A 5 38842389
2024 Au-decorated Ti3C2Tx/porous carbon immunoplatform for ECM1 breast cancer biomarker detection with machine learning computation for predictive accuracy. Talanta 5 38968654
2023 ECM1 promotes migration and invasion in endometriosis. Reproductive biology 5 37992590
2020 Gene silencing of extracellular matrix protein 1 (ECM1) results in phenotypic alterations of dermal fibroblasts reminiscent of clinical features of lichen sclerosus. Journal of dermatological science 5 33046330
2016 Treatment of lipoid proteinosis with acitretin in two patients from two unrelated Chinese families with novel nonsense mutations of the ECM1 gene. The Journal of dermatology 5 26778481
2016 Production and characterization of domain-specific monoclonal antibodies against human ECM1. Protein expression and purification 5 26826312
2016 Extracellular matrix protein 1 gene (ECM1) mutations in nine Iranian families with lipoid proteinosis. The Indian journal of medical research 5 27241643
1998 Identification, characterization, and mapping of Ecm1, a locus affecting extracellular matrix production and lesion size in Cochliobolus heterostrophus. Genome 5 9549064
2025 Human menstrual blood-derived stem cells secreted ECM1 directly interacts with LRP1α to ameliorate hepatic fibrosis through FoxO1 and mTOR signaling pathway. Stem cell research & therapy 4 40336034
2024 TRPV4 drives the progression of leiomyosarcoma by promoting ECM1 generation and co-activating the FAK/PI3K/AKT/GSK3β pathway. Cellular oncology (Dordrecht, Netherlands) 4 39612152
2015 Expression of ECM1 and MMP-2 in follicular thyroid lesions among Egyptians. Cancer biomarkers : section A of Disease markers 4 25812648
2010 Homozygous frame shift mutation in ECM1 gene in two siblings with lipoid proteinosis. Journal of dermatological case reports 4 21886756
2024 ECM1-associated miR-1260b promotes osteogenic differentiation by targeting GDI1. Acta histochemica 3 38266317
2012 A novel missense mutation in exon 7 of the ECM1 gene in an Iranian lipoid proteinosis patient. Genetics and molecular research : GMR 3 23212332
2006 [The relationship between ECM1 and the angiogenesis and metastasis of laryngeal carcinoma]. Lin chuang er bi yan hou ke za zhi = Journal of clinical otorhinolaryngology 3 16646403
2025 ECM1 expression in chronic liver disease: Regulation by EGF/STAT1 and IFNγ/NRF2 signalling. JHEP reports : innovation in hepatology 2 40671832
2024 Extracellular matrix protein 1 (ECM1) is a potential biomarker in B cell acute lymphoblastic leukemia. Clinical and experimental medicine 2 38546916
2024 A Sporadic Family of Lipoid Proteinosis with Novel ECM1 Gene Mutations. Clinical, cosmetic and investigational dermatology 2 38651074
2024 Serum ECM1 is a promising biomarker for staging and monitoring fibrosis in patients with chronic hepatitis B. Science China. Life sciences 2 39348048
2024 NTRK fusion promotes tumor migration and invasion through epithelial-mesenchymal transition and closely interacts with ECM1 and NOVA1. BMC cancer 2 39639242
2022 Lipoid proteinosis: Novel ECM1 pathogenic variants and intrafamilial variability in four unrelated Arab families. Pediatric dermatology 2 36670503
2019 Correction to: ECM1 regulates cell proliferation and trastuzumab resistance through activation of EGF-signaling. Breast cancer research : BCR 2 30914052
2014 Identification of recurrent c.742G>T nonsense mutation in ECM1 in Pakistani families suffering from lipoid proteinosis. Molecular biology reports 2 24413997
2025 Association between extracellular matrix protein 1 (ECM1) gene polymorphisms (rs3834087 and rs3754217) and Hepatitis B Virus evolution in an African cohort. Cellular and molecular biology (Noisy-le-Grand, France) 1 39799499
2025 Opportunities and Risks of Promoting Skin and Bone Healing via Implant Biofunctionalization of Extracellular Matrix Protein ECM1. Journal of functional biomaterials 1 41149731
2026 H19 enhances pancreatic cancer proliferation and invasion by reducing miR-29c-5p's inhibitory effects on ATF2/ECM1. Scientific reports 0 41651902
2026 ECM1 produced by hepatic stellate cells serves as a gatekeeper of liver homeostasis in hepatic fibrosis. Hepatology (Baltimore, Md.) 0 41854361
2026 Oral and maxillofacial manifestations of lipoid proteinosis with a novel ECM1 mutation: case report and literature review. Oral surgery, oral medicine, oral pathology and oral radiology 0 41927423
2026 Extracellular vesicle delivery of Myricetin suppresses ovarian cancer through mitochondrial dynamics by downregulating the ECM1/NF-κB/TGFβ signaling pathway. Scientific reports 0 41986409
2025 Identification and validation of ECM1 as a causal plasma biomarker in knee osteoarthritis through proteome-wide association study and bioinformatics. Medicine 0 40859530
2025 The correlation between serum ECM1 and cardiac fibrosis in heart failure patients. BMC cardiovascular disorders 0 41361743
2023 Lipoid Proteinosis: Identification of a Novel Nonsense Mutation c.1246C>T:p.R416X in ECM1 gene from Bangladesh. Pakistan journal of medical sciences 0 37492299
2020 Identification of a novel three-nucleotide duplication in ECM1 in Chinese siblings affected with lipoid proteinosis. Clinica chimica acta; international journal of clinical chemistry 0 33159951

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