Affinage

MMP7

Matrilysin · UniProt P09237

Length
267 aa
Mass
29.7 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MMP7 (matrilysin/PUMP-1) is a secreted zinc-dependent metalloendopeptidase that, despite lacking the hemopexin-like domain of classical collagenases, is produced as a latent zymogen, activated to ~21/19 kDa forms, and degrades a broad range of extracellular substrates including casein, gelatins, fibronectin, and fibronectin aggregates (PMID:2550050, PMID:29600597). Beyond bulk ECM turnover, MMP7 executes regulatory proteolysis of specific bioactive substrates: it sheds the syndecan-1 ectodomain to lower α2β1 integrin affinity and permit epithelial wound closure (PMID:19668337), cleaves perlecan/HSPG2 domain IV to convert tumor cells from a clustered to a dispersed invasive phenotype (PMID:24833109), degrades soluble VEGFR-1 to liberate VEGF and restore VEGFR-2 signaling and endothelial tube formation (PMID:18974372), and cleaves galectin-3 to suppress epithelial migration (PMID:20812334). MMP7 also acts as an upstream activator of other proteases, processing proADAM28s, dissociating and activating proMMP-2 from its TIMP-2 complex, and activating latent collagenase (PMID:2550050, PMID:15013428, PMID:15523695). Its proteolysis extends to cell-surface and intracellular targets controlling cell fate and signaling: shedding of Fas confers oxaliplatin resistance in p53-deficient colon cancer (PMID:19266094), cleavage of nucleolin at Asp255 generates a truncated form that stabilizes oncogenic mRNAs to promote metastasis (PMID:24632608), and disruption of the E-cadherin/β-catenin complex drives EMT (PMID:27375020). Transcriptionally, MMP7 is a convergent effector of β-catenin/TCF-Lef, STAT3, AP-1 (c-Jun/c-Fos), CREB, and FOXC1 inputs that integrate Wnt, HER2-STAT3, IL-17, β2-adrenergic, and inflammatory signals (PMID:15457508, PMID:18411043, PMID:20939893, PMID:30303742, PMID:25847246, PMID:29249801), positioning it as a required driver of pancreatic, prostate, and breast cancer progression (PMID:21481787, PMID:27375020, PMID:29249801). In tissue homeostasis and injury it degrades nephrin downstream of tubular β-catenin to cause proteinuria (PMID:31743113) and processes pro-α-defensins in Paneth cells (PMID:32359121).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1989 High

    Establishing MMP7 as a bona fide latent metalloproteinase defined its catalytic identity and substrate range despite its atypically minimal domain structure lacking the hemopexin module of classical collagenases.

    Evidence COS-cell expression with in vitro protease and autocleavage assays plus EDTA/phenanthroline/TIMP inhibition

    PMID:2550050

    Open questions at the time
    • In vivo physiological activator not identified
    • Endogenous tissue substrates inferred only from in vitro casein/gelatin/fibronectin cleavage
  2. 2004 High

    Showing MMP7 activates proADAM28s and that TCF binding element position dictates Lef-1 activator-versus-repressor behavior established MMP7 both as an upstream protease in a proteolytic cascade and as a context-dependent Wnt/β-catenin transcriptional target.

    Evidence In vitro reconstitution of proADAM28s activation with inhibitor controls; promoter-luciferase reporters with TBE mutagenesis and gel-shift affinity measurement

    PMID:15013428 PMID:15457508

    Open questions at the time
    • Physiological relevance of the MMP7→ADAM28s→IGFBP-3 axis in vivo not tested
    • TBE rules derived from reporter constructs, not native chromatin
  3. 2005 High

    Demonstrating that MMP7 dissociates and activates proMMP-2 from the MMP-2/TIMP-2 complex placed MMP7 upstream of the gelatinases in driving cancer cell invasion.

    Evidence In vitro progelatinase activation, co-immunoprecipitation, and Transwell invasion with TIMP-2 rescue in ovarian cancer cells

    PMID:15523695

    Open questions at the time
    • Genetic confirmation of the MMP7→MMP-2 axis in vivo absent
    • Stoichiometry of complex dissociation not resolved
  4. 2008 High

    Identifying sVEGFR-1 as a substrate and demonstrating HER2/HRG-driven STAT3 promoter occupancy connected MMP7 proteolysis to angiogenic VEGF liberation and to oncogenic transcriptional control.

    Evidence Recombinant degradation assays with tube-formation/migration/VEGFR-2 phosphorylation readouts (Blood); ChIP and promoter mutagenesis with STAT3C phenocopy (MCF-7)

    PMID:18411043 PMID:18974372

    Open questions at the time
    • In vivo angiogenic consequence of sVEGFR-1 cleavage not established
    • Relative contribution of STAT3 versus other promoter inputs context-dependent
  5. 2009 High

    Knockout evidence that MMP7 sheds syndecan-1 to lower α2β1 integrin affinity defined a non-ECM regulatory proteolysis mechanism enabling epithelial wound closure.

    Evidence Mmp7−/− mice with in vitro/in vivo epithelial wound assays and integrin affinity measurement; recombinant MMP7 Fas-shedding studies in resistant colon cancer

    PMID:19266094 PMID:19668337

    Open questions at the time
    • Mechanism by which syndecan-1 shedding alters integrin conformation not structurally defined
    • Fas-shedding p53-dependence mechanism unresolved (Medium-confidence)
  6. 2010 High

    Cleavage of galectin-3 and identification of AP-1/STAT3 cooperative promoter occupancy under β2-adrenergic stimulation broadened both the substrate repertoire and the upstream signaling inputs to MMP7.

    Evidence In vitro cleavage with N-terminal sequencing/MS and scratch-wound assay; promoter mutagenesis with STAT3/c-Jun Co-IP and β2-AR antagonist in gastric cancer

    PMID:20812334 PMID:20939893

    Open questions at the time
    • In vivo significance of galectin-3 fragments not shown
    • Whether STAT3 acts only as a c-Jun co-factor at the AP-1 site generalizes beyond gastric cells unknown
  7. 2011 High

    Genetic epistasis placed MMP7 as a required STAT3-dependent effector of Kras-driven pancreatic cancer progression, moving it from in vitro correlate to in vivo driver.

    Evidence Kras-driven mouse PDA model with Stat3 and Mmp7 conditional KOs and tumor/metastasis quantification

    PMID:21481787

    Open questions at the time
    • Critical MMP7 substrate(s) mediating PDA progression not defined
    • AP-1-driven H2O2 induction in CRC (Medium) extends but does not confirm pathway breadth
  8. 2014 High

    Pinpointing MMP7 cleavage of perlecan domain IV and of nucleolin at Asp255 revealed distinct mechanisms—BM remodeling for dispersal versus generation of a truncated RNA-stabilizing fragment—linking MMP7 to invasion and metastasis.

    Evidence In vitro cleavage of purified perlecan with invasion assays; cleavage-site mapping plus mRNA-stability and 3'-UTR binding assays downstream of EGFR

    PMID:24632608 PMID:24833109

    Open questions at the time
    • Truncated nucleolin (TNCL) function relies on in vitro cleavage; in vivo abundance not quantified
    • Full repertoire of TNCL-stabilized mRNAs incomplete
  9. 2015 Medium

    Convergent transcriptional studies established FOXC1 (directly and via WNT5A/NF-κB and β-catenin), LEF-1, CREB, and PKP3/PRL3 loss as upstream MMP7 regulators that funnel into invasion programs.

    Evidence siRNA/overexpression with invasion assays, ChIP, EMSA, casein zymography, allele-specific CREB ChIP, and shRNA xenograft models across breast, gastric, and other cancers

    PMID:22645147 PMID:22686279 PMID:24143235 PMID:25847246 PMID:25875355

    Open questions at the time
    • Most regulatory links are single-lab
    • Interplay/hierarchy among FOXC1, β-catenin, and NF-κB inputs at the MMP7 locus not unified
    • Allele-specific CREB regulation (Medium) not independently confirmed
  10. 2016 High

    Demonstrating MMP7 disrupts the E-cadherin/β-catenin complex to drive IL-17-dependent EMT, and that nuclear MMP7 physically binds ARF, expanded its roles into EMT control and an unexpected nuclear interaction.

    Evidence Mmp7/Pten double-KO mice, IL-17 stimulation with siRNA and inhibitor (prostate cancer); Co-IP and nuclear co-localization with ARF gain/loss-of-function

    PMID:27356744 PMID:27375020

    Open questions at the time
    • Nuclear MMP7-ARF mechanism (Medium) lacks reciprocal validation and catalytic requirement is unclear
    • How a secreted protease accesses the nucleus unresolved
  11. 2018 High

    Identifying MMP7 cleavage of fibronectin aggregates in demyelination and cortisol/AP-1-driven COL4A5 degradation in amnion connected MMP7 to lesion clearance and tissue remodeling in non-cancer contexts.

    Evidence In vitro fibronectin-aggregate cleavage with lysolecithin demyelination model and MS lesion staining; RNA-seq, ChIP of c-Fos/c-Jun, siRNA, and neutralizing antibody in amnion fibroblasts

    PMID:29600597 PMID:30303742

    Open questions at the time
    • Causal contribution of MMP7 to remyelination outcomes not demonstrated by genetic loss-of-function
    • Physiological role of amnion COL4A5 degradation in membrane rupture not directly tested
  12. 2019 High

    Showing tubular β-catenin drives MMP7 secretion that directly cleaves nephrin established a defined β-catenin→MMP7→nephrin axis causing proteinuria and glomerular injury.

    Evidence Tubule-specific β-catenin KO, Mmp7 KO, ex vivo glomerular and cell-free nephrin cleavage assays, and in vivo MMP7 infusion/overexpression

    PMID:31743113

    Open questions at the time
    • Whether nephrin cleavage is the sole mediator of injury not isolated
    • Earlier Wnt4/MMP7 co-localization (Low) provides only correlative upstream context
  13. 2020 Medium

    Placing MMP7 in the Paneth-cell Mmp7/α-defensin axis disrupted by high-fat diet extended its physiological role to innate antimicrobial peptide processing.

    Evidence NT knockout mice, high-fat diet model, PKCτ shRNA/inhibitors, and NF-κB/DEFA5 readouts

    PMID:32359121

    Open questions at the time
    • Direct MMP7 cleavage of pro-α-defensins not reconstituted in this study
    • Single-lab pathway placement
  14. 2023 Medium

    Linking F. nucleatum infection to MMP7 induction via JNK-AP1 added a microbial inflammatory input to the AP-1 transcriptional control of MMP7 in colorectal cancer.

    Evidence Wound-healing/Transwell migration with JNK/AP-1 inhibition and knockdown

    PMID:37814323

    Open questions at the time
    • No in vivo validation
    • Direct AP-1 occupancy at MMP7 promoter not shown in this context

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MMP7 zymogen activation is controlled in vivo, which of its many substrates dominate in each tissue context, and the structural/mechanistic basis of its reported nuclear ARF interaction remain unresolved.
  • No in vivo physiological pro-MMP7 activator identified
  • Tissue-specific dominant substrate not deconvoluted from the broad in vitro repertoire
  • Mechanism of secreted-protease nuclear access and ARF binding undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 10 GO:0140096 catalytic activity, acting on a protein 8
Localization
GO:0005576 extracellular region 5 GO:0005634 nucleus 1
Pathway
R-HSA-1474244 Extracellular matrix organization 5 R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 3

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 MMP7 (PUMP-1) is a latent secreted metalloproteinase that, despite lacking the hemopexin-like domain of classical collagenases, is activated by organomercurial compounds (APMA) and degrades casein, type I/III/IV/V gelatins, fibronectin, and can activate latent collagenase in vitro. Active forms of 21,000 and 19,000 Da are generated upon activation. Activity is inhibited by EDTA, 1,10-phenanthroline, and TIMP. COS cell expression, IgG-Sepharose pulldown, in vitro protease assay, autocleavage assay, inhibitor studies Biochemistry High 2550050
2004 MMP-7 activates proADAM28s (65 kDa) to produce active 42- and 40-kDa forms. Active ADAM28s then cleaves insulin-like growth factor binding protein-3 (IGFBP-3) in both free and IGF-bound forms; this cleavage is blocked by EDTA, 1,10-phenanthroline, KB-R7785, TIMP-3, and TIMP-4. In vitro protease assay, recombinant protein incubation, inhibitor studies Biochemical and biophysical research communications High 15013428
2005 MMP-7 promotes invasion of ovarian cancer cells by activating proMMP-2 and proMMP-9. MMP-7 can dissociate MMP-2 from the MMP-2/TIMP-2 complex and activate it in a time-dependent, concentration-dependent manner in vitro. TIMP-2 inhibits both proMMP-2 activation and MMP-7-induced increased invasion. In vitro progelatinase activation assay, co-immunoprecipitation, Transwell invasion assay, recombinant MMP-7 treatment International journal of cancer High 15523695
2008 MMP-7 degrades soluble VEGFR-1 (sVEGFR-1/sFlt-1), liberating VEGF165 from the sVEGFR-1 complex and increasing VEGF bioavailability. This degradation abrogates sVEGFR-1 inhibition of VEGFR-2 phosphorylation on endothelial cells and promotes tube formation and migration. In vitro degradation assay with recombinant proteins, co-immunoprecipitation (HUVECs), tube formation assay, migration assay, VEGFR-2 phosphorylation assay Blood High 18974372
2009 MMP7 sheds syndecan-1 from lung epithelial cells upon injury; this shedding is absent in Mmp7−/− mice. MMP7-mediated syndecan-1 shedding facilitates wound closure by causing the α2β1 integrin to assume a less active conformation, removing restrictions to cell migration. Mmp7−/− knockout mouse model, in vitro and in vivo epithelial wound assay, integrin affinity state measurement, syndecan-1 shedding detection PloS one High 19668337
2010 MMP7 (matrilysin-1) directly cleaves galectin-3 in vitro, producing three fragments (20.2, 18.9, and 15.5 kDa). Recombinant MMP7 treatment of colonic epithelial T84 cells produces galectin-3 cleavage fragments in the supernatant and inhibits cell migration and wound closure; galectin-3's pro-migratory effect is abrogated by MMP7 co-treatment. In vitro cleavage assay, N-terminal sequencing, mass spectrometry, Western blotting, in vitro scratch wound assay Inflammatory bowel diseases High 20812334
2014 MMP7 cleaves purified perlecan/HSPG2 at multiple sites within domain IV in vitro, including when perlecan is decorated with heparan sulfate or embedded in native BM context. MMP7 digestion of perlecan domain IV fragment (Dm IV-3) reverses cell clustering to a cell dispersion phenotype in metastatic PCa cells and increases invasion through perlecan-rich BM extract. In vitro protease assay with purified perlecan, in silico cleavage prediction, Transwell invasion assay with MMP-7-pre-digested BM extract Matrix biology High 24833109
2014 MMP7 cleaves nucleolin (NCL) at Asp255 to generate a C-terminal truncated form (TNCL, ~55 kDa). TNCL stabilizes MMP9 mRNA (and other oncogenic mRNAs) by binding to their 3'-UTRs, thereby promoting metastasis. This cleavage is induced downstream of EGF receptor pathway activation. MMP7 in vitro cleavage assay identifying cleavage site, Western blot, mRNA stability assay, 3'-UTR binding, cell invasion assay Oncogene High 24632608
2019 β-catenin signaling in renal tubular cells drives MMP-7 expression and secretion. Secreted MMP-7 directly degrades nephrin (a key slit diaphragm protein) in a proteolytic-activity-dependent manner in cultured glomeruli and cell-free systems, causing proteinuria and glomerular injury in vivo. Conditional tubule-specific β-catenin KO mice, MMP-7 genetic ablation (KO mice), ex vivo glomerular incubation with recombinant MMP-7, cell-free nephrin cleavage assay, in vivo MMP-7 infusion/overexpression JCI insight High 31743113
2018 MMP7 cleaves fibronectin aggregates in vitro, producing a prominent 13 kDa EIIIA-containing fragment. MMP7 is upregulated in lysolecithin-induced demyelination (endogenous clearance), whereas proMMP7 levels are substantially reduced in chronic active and inactive MS lesions. IL-4-activated microglia/macrophages are major cellular sources of proMMP7. In vitro fibronectin aggregate cleavage assay, Western blot, lysolecithin demyelination mouse model, immunostaining of MS lesions, macrophage polarization assays Glia High 29600597
2011 Stat3 signaling enforces MMP7 expression in pancreatic ductal adenocarcinoma (PDA) cells. MMP7 deletion in a Kras-driven mouse model limits tumor size and metastasis, placing MMP7 downstream of Stat3 as a required effector of PDA progression. Genetic epistasis in Kras-driven mouse PDA model, Stat3 conditional KO, Mmp7 KO mice, tumor size/metastasis quantification Cancer cell High 21481787
2004 The position of Tcf binding elements (TBEs) relative to the MMP7 transcriptional start site determines whether Lef-1 acts as an activator or repressor of β-catenin-driven MMP7 transcription. Upstream TBEs (human promoter) allow Lef-1 activation, whereas a downstream TBE (mouse promoter) supports Lef-1-mediated repression. TBE sequence affinity for Lef-1 determines potency: high-affinity sites (G·C at 5′/3′ ends) yield up to 115-fold greater β-catenin responsiveness. Promoter-luciferase reporter assays, TBE mutagenesis, in vitro Lef-1 binding affinity (gel-shift), heterologous promoter constructs Molecular carcinogenesis High 15457508
2008 HER2 overexpression or HRG stimulation upregulates MMP-7 transcription and protein secretion via activated STAT3. STAT3 binds directly to the MMP-7 promoter at a critical STAT3 binding element, as shown by ChIP and promoter mutagenesis. Constitutively active STAT3 is sufficient to drive MMP-7 expression. Stable HER2/STAT3C overexpression in MCF-7, promoter-luciferase assay, ChIP, STAT3 binding site mutagenesis, RT-PCR, Western blot Cellular signalling High 18411043
2015 FOXC1 induces MMP7 expression and MMP7-dependent invasion in basal-like breast cancer cells. Silencing FOXC1 selectively decreases MMP7 without reducing other MMPs; ectopic FOXC1 in non-transformed cells increases MMP7 and invasion in an MMP7-dependent manner. siRNA knockdown, transient overexpression, Matrigel invasion assay, mRNA/protein expression analysis The Journal of biological chemistry Medium 22645147
2017 FOXC1 directly binds the WNT5A promoter to activate its expression; WNT5A then activates NF-κB signaling to induce MMP7 expression. The FOXC1→WNT5A→NF-κB→MMP7 axis is required for TNBC cell invasiveness in vitro and lung metastasis in vivo (MMP7 overexpression rescues WNT5A-KO metastasis defect). ChIP (FOXC1 binding to WNT5A promoter), enChIP-MS, WNT5A knockout xenograft model, MMP7 overexpression rescue, NF-κB pathway inhibition Oncogene High 29249801
2016 MMP7 promotes prostate adenocarcinoma by disrupting the E-cadherin/β-catenin complex to upregulate EMT transcription factors. MMP7 knockout in Pten-null mice limits EMT characteristics, recapitulating the phenotype of IL-17 receptor C/Pten double-KO mice. IL-17 induces MMP7 and EMT in human prostate cancer cells; MMP7 siRNA knockdown inhibits IL-17-induced EMT. Mmp7/Pten double KO mice, siRNA knockdown, MMP7 inhibitor (Compound III) in vivo, Western blot for E-cadherin/β-catenin Oncogene High 27375020
2010 Catecholamine (isoproterenol) stimulation via β2-adrenergic receptor upregulates MMP-7 expression in gastric cancer cells through AP-1 (dominant pathway) and STAT3 transcription factors. STAT3 and c-Jun physically interact and co-occupy the AP-1 site in the MMP-7 promoter; AP-1 site mutation completely abolishes isoproterenol-induced MMP-7 promoter activity, whereas STAT3-site mutation alone does not. Promoter-luciferase reporter assay, site-directed mutagenesis of AP-1 and STAT3 sites, siRNA knockdown, Co-IP (STAT3/c-Jun interaction), β2-AR antagonist treatment Molecular cancer High 20939893
2008 Activin A enhances MMP-7 expression via the AP-1 transcription factor (not through Smad2/3). Mutation of the AP-1 binding site in the MMP-7 promoter reduces activity, whereas mutation of the Smad binding site does not. c-Jun is increased in activin A-expressing esophageal carcinoma cells. Stable transfection of activin βA, promoter-luciferase assay with AP-1 and Smad site mutations, RT-PCR, Northern blot, neutralizing antibody International journal of oncology Medium 18695873
2015 FOXC1 promotes MMP7-dependent invasion in TNBC via β-catenin activation of MMP7. Wnt-β-catenin signaling upregulates MMP7 in a PTEN-loss-dependent manner; pharmacological/siRNA attenuation of β-catenin downregulates secreted MMP7 enzymatic activity (casein zymography). siRNA knockdown of β-catenin, WP inhibitors (XAV939, sulindac sulfide), LY294002 (PTEN mimetic), casein zymography, Western blot PloS one Medium 24143235
2007 Gastrin stimulates MMP-7 promoter-luciferase activity in gastric epithelial cells. MMP-7 secreted by gastric epithelial cells promotes myofibroblast proliferation via MAPK and PI3K pathways; neutralizing antibodies to MMP-7 block this proliferation. Promoter-luciferase reporter assay, MMP-7 neutralizing antibody, conditioned medium treatment of myofibroblasts, pathway inhibitors (MAPK/PI3K) American journal of physiology. Gastrointestinal and liver physiology Medium 17218472
2015 MMP7 knockdown in PKP3 (Plakophilin3)-deficient cells abolishes in vitro cell migration/invasion and in vivo tumor formation. Increased MMP7 levels upon PKP3 loss are mediated by elevated PRL3 (Phosphatase of Regenerating Liver-3). shRNA knockdown of MMP7, Transwell migration/invasion assay, mouse xenograft tumor formation, Western blot for PRL3/MMP7 PloS one Medium 25875355
2016 MMP7 physically binds ARF (p14ARF/p19Arf) and co-localizes with it in the nucleus of malignant prostate tumor cells. ARF knockdown markedly reduces MMP7 levels; inducible ARF expression increases MMP7 and decreases E-cadherin. Co-expression of ARF and MMP7 promotes cell migration. Co-immunoprecipitation, co-localization (nuclear fractionation/immunofluorescence), inducible ARF overexpression, shRNA knockdown, mouse Pten/Trp53/p19Arf triple mutant model Oncotarget Medium 27356744
2018 Cortisol induces MMP7 expression in human amnion fibroblasts via AP-1 (c-Fos and c-Jun). ChIP shows enrichment of c-Fos and c-Jun at the AP-1 binding site in the MMP7 promoter following cortisol treatment. MMP7 secreted under cortisol stimulation degrades extracellular COL4A5 (collagen IV α5 chain), which is blocked by anti-MMP-7 antibody. RNA-sequencing, RT-qPCR, Western blot, ChIP (c-Fos/c-Jun at MMP7 promoter AP-1 site), siRNA knockdown of c-Fos/c-Jun, anti-MMP-7 neutralizing antibody, amnion tissue analysis FASEB journal High 30303742
2015 Nicotine increases MMP7 expression in gastric adenocarcinoma cells by enhancing CREB phosphorylation and nuclear translocation. Phosphorylated CREB preferentially binds the -181G allele of the MMP7 promoter relative to -181A (ChIP assay), conferring allele-specific transcriptional upregulation. Promoter-reporter assay, ChIP (phospho-CREB binding to -181G vs -181A allele), CREB overexpression, Western blot, case-control genotyping The Journal of biological chemistry Medium 25847246
2009 MMP7 promotes resistance to oxaliplatin by shedding Fas receptor from the plasma membrane of resistant colon cancer cells. Inhibition of MMP7 (by 1,10-phenanthroline or siRNA) restores Fas surface levels and re-sensitizes cells to oxaliplatin-induced apoptosis in p53-mutant or p53-null but not p53-wildtype backgrounds. siRNA knockdown, MMP inhibitor (1,10-phenanthroline), flow cytometry (surface Fas), apoptosis assay, oxaliplatin-resistant cell line models PloS one Medium 19266094
2012 LEF-1 directly binds the MMP-7 promoter region (demonstrated by EMSA) and positively regulates MMP-7 transcription. LEF-1 siRNA knockdown in breast cancer cells decreases MMP-7 expression and causes G2/M cell cycle arrest. EMSA (in vitro DNA-protein binding), siRNA knockdown, RT-PCR, Western blot, cell cycle analysis Genes to cells Medium 22686279
2011 H2O2-induced MMP-7 expression in colorectal cancer cells is mediated by MAPK signaling through JNK/c-Jun and ERK/c-Fos activation in an AP-1-dependent manner. AP-1 pathway activation is required for H2O2-driven MMP-7 gene transcription and cell invasion. MAPK inhibitor studies (JNK, ERK, p38), AP-1 reporter assay, siRNA/inhibitor-based pathway dissection, cell invasion assay International journal of biological sciences Medium 21814482
2004 MMP-7 expression in the kidney is induced during renal injury and closely parallels the expression pattern of Wnt4, consistent with Wnt4-driven regulation of matrilysin expression in tubular injury and progression to tubulointerstitial fibrosis. Northern blotting, RNase protection assay (RPA), immunohistochemistry, in situ hybridization; expression co-localization in three renal injury mouse models Kidney international Low 15149334
1996 The MMP7 gene (matrilysin) maps to human chromosome 11q21→q22 by somatic cell hybrid analysis and in situ hybridization, placing it within the known cluster of matrix metalloproteinase genes. Southern blot, PCR analysis of somatic cell hybrids, fluorescence in situ hybridization (FISH) Cytogenetics and cell genetics Medium 8978768
2020 MMP7 is required for processing pro-α-defensins in Paneth cells via the Mmp7/α-defensin axis; high-fat diet disrupts this axis, and NT deficiency prevents its disruption. NT inhibits DEFA5 (α-defensin 5) expression through atypical PKCτ/λ-mediated suppression of NF-κB signaling in Paneth cells. NT knockout mice, high-fat diet model, shRNA knockdown (PKCτ), PKC inhibitors, NF-κB reporter, DEFA5 expression analysis FASEB journal Medium 32359121
2023 F. nucleatum infection upregulates MMP7 in colorectal cancer cells via the MAPK(JNK)-AP1 axis, promoting cell migration in vitro. Wound healing and Transwell migration assays, JNK/AP-1 pathway inhibition, Western blot, gene knockdown Journal of translational medicine Medium 37814323

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis. PLoS medicine 475 18447576
2011 Stat3 and MMP7 contribute to pancreatic ductal adenocarcinoma initiation and progression. Cancer cell 437 21481787
1991 Expression and localization of the matrix metalloproteinase pump-1 (MMP-7) in human gastric and colon carcinomas. Molecular carcinogenesis 267 1793490
1989 Pump-1 cDNA codes for a protein with characteristics similar to those of classical collagenase family members. Biochemistry 225 2550050
2003 MT1-MMP and MMP-7 in invasion and metastasis of human cancers. Cancer metastasis reviews 188 12784993
2016 Interleukin-17 promotes prostate cancer via MMP7-induced epithelial-to-mesenchymal transition. Oncogene 161 27375020
2009 Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer. International journal of colorectal disease 161 19421758
2005 Matrilysin (MMP-7) promotes invasion of ovarian cancer cells by activation of progelatinase. International journal of cancer 149 15523695
1993 Expression of MMP-7(PUMP-1) mRNA in human colorectal cancers. International journal of cancer 137 8514452
2004 Differential expression of matrilysin-1 (MMP-7), 92 kD gelatinase (MMP-9), and metalloelastase (MMP-12) in oral verrucous and squamous cell cancer. The Journal of pathology 136 14694517
2013 DKK1 promotes hepatocellular carcinoma cell migration and invasion through β-catenin/MMP7 signaling pathway. Molecular cancer 122 24325363
2021 Roles of matrix metalloproteinase-7 (MMP-7) in cancer. Clinical biochemistry 112 33713636
2009 MMP7 shedding of syndecan-1 facilitates re-epithelialization by affecting alpha(2)beta(1) integrin activation. PloS one 104 19668337
2014 MiRNA-34a inhibits EGFR-signaling-dependent MMP7 activation in gastric cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 103 24981249
2016 Sphingosine-1-phosphate induced epithelial-mesenchymal transition of hepatocellular carcinoma via an MMP-7/ syndecan-1/TGF-β autocrine loop. Oncotarget 102 27556509
2003 Levels and molecular forms of MMP-7 (matrilysin-1) and MMP-8 (collagenase-2) in diseased human peri-implant sulcular fluid. Journal of periodontal research 98 14632921
2004 ADAM28 is activated by MMP-7 (matrilysin-1) and cleaves insulin-like growth factor binding protein-3. Biochemical and biophysical research communications 95 15013428
2019 SREBP1 promotes the invasion of colorectal cancer accompanied upregulation of MMP7 expression and NF-κB pathway activation. BMC cancer 94 31299935
2014 CXCL4-induced plaque macrophages can be specifically identified by co-expression of MMP7+S100A8+ in vitro and in vivo. Innate immunity 91 24663337
2010 Catecholamine up-regulates MMP-7 expression by activating AP-1 and STAT3 in gastric cancer. Molecular cancer 87 20939893
2006 Enhanced expression of MMP-7 and MMP-13 in inflammatory bowel disease: a precancerous potential? Inflammatory bowel diseases 84 17075343
2004 Matrilysin (MMP-7) expression in renal tubular damage: association with Wnt4. Kidney international 84 15149334
2008 Degradation of soluble VEGF receptor-1 by MMP-7 allows VEGF access to endothelial cells. Blood 83 18974372
2013 miR-126&126* restored expressions play a tumor suppressor role by directly regulating ADAM9 and MMP7 in melanoma. PloS one 81 23437250
2004 Collagenase-1 (MMP-1), matrilysin-1 (MMP-7), and stromelysin-2 (MMP-10) are expressed by migrating enterocytes during intestinal wound healing. Scandinavian journal of gastroenterology 79 15545168
2001 Upregulation and differential expression of matrilysin (MMP-7) and metalloelastase (MMP-12) and their inhibitors TIMP-1 and TIMP-3 in Barrett's oesophageal adenocarcinoma. British journal of cancer 77 11487270
2012 The forkhead box transcription factor FOXC1 promotes breast cancer invasion by inducing matrix metalloprotease 7 (MMP7) expression. The Journal of biological chemistry 76 22645147
2011 Dimerumic acid inhibits SW620 cell invasion by attenuating H₂O₂-mediated MMP-7 expression via JNK/C-Jun and ERK/C-Fos activation in an AP-1-dependent manner. International journal of biological sciences 75 21814482
2009 The role of MMP7 and its cross-talk with the FAS/FASL system during the acquisition of chemoresistance to oxaliplatin. PloS one 72 19266094
2013 Differential activation of Wnt-β-catenin pathway in triple negative breast cancer increases MMP7 in a PTEN dependent manner. PloS one 68 24143235
2017 FOXC1-induced non-canonical WNT5A-MMP7 signaling regulates invasiveness in triple-negative breast cancer. Oncogene 67 29249801
2019 Circular RNA hsa_circRNA_0007334 is Predicted to Promote MMP7 and COL1A1 Expression by Functioning as a miRNA Sponge in Pancreatic Ductal Adenocarcinoma. Journal of oncology 65 31428151
2017 Nuclear Drosha enhances cell invasion via an EGFR-ERK1/2-MMP7 signaling pathway induced by dysregulated miRNA-622/197 and their targets LAMC2 and CD82 in gastric cancer. Cell death & disease 65 28252644
2014 Matrilysin/matrix metalloproteinase-7(MMP7) cleavage of perlecan/HSPG2 creates a molecular switch to alter prostate cancer cell behavior. Matrix biology : journal of the International Society for Matrix Biology 63 24833109
2015 Placental growth factor promotes metastases of ovarian cancer through MiR-543-regulated MMP7. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 62 26402225
2016 Expressions of Matrix Metalloproteinases (MMP-2, MMP-7, and MMP-9) and Their Inhibitors (TIMP-1, TIMP-2) in Inflammatory Bowel Diseases. Gastroenterology research and practice 61 27034654
2010 Matrilysin-1 (MMP7) cleaves galectin-3 and inhibits wound healing in intestinal epithelial cells. Inflammatory bowel diseases 61 20812334
2006 Genetic polymorphisms of MMP1, MMP3 and MMP7 gene promoter and risk of colorectal adenoma. BMC cancer 59 17125518
2009 Expression of MMP-7, MMP-9, TIMP-1 and TIMP-2 mRNA in lung tissue of patients with non-small cell lung cancer (NSCLC) and benign pulmonary disease. Anticancer research 57 19596921
2018 Celastrol inhibits colorectal cancer cell proliferation and migration through suppression of MMP3 and MMP7 by the PI3K/AKT signaling pathway. Anti-cancer drugs 55 29553945
2019 DKK1 inhibits breast cancer cell migration and invasion through suppression of β-catenin/MMP7 signaling pathway. Cancer cell international 51 31285694
2019 Tubular injury triggers podocyte dysfunction by β-catenin-driven release of MMP-7. JCI insight 51 31743113
1999 The matrix metalloprotease pump-1 (MMP-7, Matrilysin): A candidate marker/target for ovarian cancer detection and treatment. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 51 10050107
2012 Secreted protein acidic and rich in cysteine (SPARC) suppresses angiogenesis by down-regulating the expression of VEGF and MMP-7 in gastric cancer. PloS one 50 22957090
2007 Increased gastric expression of MMP-7 in hypergastrinemia and significance for epithelial-mesenchymal signaling. American journal of physiology. Gastrointestinal and liver physiology 50 17218472
2003 Role of PTEN and MMP-7 expression in growth, invasion, metastasis and angiogenesis of gastric carcinoma. Pathology international 47 14516315
2014 Dual MMP7-proximity-activated and folate receptor-targeted nanoparticles for siRNA delivery. Biomacromolecules 46 25414930
2004 Expression of heparanase gene, CD44v6, MMP-7 and nm23 protein and their relationship with the invasion and metastasis of gastric carcinomas. World journal of gastroenterology 46 15040016
2016 Rab11-FIP2 promotes colorectal cancer migration and invasion by regulating PI3K/AKT/MMP7 signaling pathway. Biochemical and biophysical research communications 43 26792722
2008 The expression of MMP-2, MMP-7, MMP-9, and TIMP-1 in chronic rhinosinusitis and nasal polyposis. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 43 18656717
2004 Tcf binding sequence and position determines beta-catenin and Lef-1 responsiveness of MMP-7 promoters. Molecular carcinogenesis 43 15457508
2013 Glutamate acid decarboxylase 1 promotes metastasis of human oral cancer by β-catenin translocation and MMP7 activation. BMC cancer 42 24261884
2014 Inhibition of epidermal growth factor receptor signaling prohibits metastasis of gastric cancer via downregulation of MMP7 and MMP13. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 41 25085584
2019 Sex determining region Y-box 12 (SOX12) promotes gastric cancer metastasis by upregulating MMP7 and IGF1. Cancer letters 40 30922917
2015 MMP7 is required to mediate cell invasion and tumor formation upon Plakophilin3 loss. PloS one 40 25875355
2023 Fusobacterium nucleatum upregulates MMP7 to promote metastasis-related characteristics of colorectal cancer cell via activating MAPK(JNK)-AP1 axis. Journal of translational medicine 39 37814323
2013 MMP-7 and TIMP-1, new targets in predicting poor wound healing in apical periodontitis. Journal of endodontics 39 23953287
2015 Raf/ERK/Nrf2 signaling pathway and MMP-7 expression involvement in the trigonelline-mediated inhibition of hepatocarcinoma cell migration. Food & nutrition research 38 26699938
2005 Quantitative estimation of matrix metalloproteinases 2 and 7 (MMP-2, MMP-7) and tissue inhibitors of matrix metalloproteinases 1 and 2 (TIMP-1, TIMP-2) in colorectal carcinoma tissue samples. Anticancer research 38 16101153
2018 Placental growth factor reverses decreased vascular and uteroplacental MMP-2 and MMP-9 and increased MMP-1 and MMP-7 and collagen types I and IV in hypertensive pregnancy. American journal of physiology. Heart and circulatory physiology 36 29569955
2013 COX-2, MMP-7 expression in oral lichen planus and oral squamous cell carcinoma. Asian Pacific journal of tropical medicine 36 23790336
2014 MMP7-mediated cleavage of nucleolin at Asp255 induces MMP9 expression to promote tumor malignancy. Oncogene 35 24632608
2014 MMP7 expression in colorectal tumours of different stages. In vivo (Athens, Greece) 33 24425843
2005 Matrilysins-1 and -2 (MMP-7 and -26) and metalloelastase (MMP-12), unlike MMP-19, are up-regulated in necrotizing enterocolitis. Journal of pediatric gastroenterology and nutrition 33 15625428
2009 Downregulation of SFRP5 expression and its inverse correlation with those of MMP-7 and MT1-MMP in gastric cancer. BMC cancer 32 19586554
2020 The Behavior of MMP-2, MMP-7, MMP-9, and Their Inhibitors TIMP-1 and TIMP-2 in Adenoma-Colorectal Cancer Sequence. Digestive diseases (Basel, Switzerland) 31 32961536
2015 Association of MMP7 -181A→G Promoter Polymorphism with Gastric Cancer Risk: INFLUENCE OF NICOTINE IN DIFFERENTIAL ALLELE-SPECIFIC TRANSCRIPTION VIA INCREASED PHOSPHORYLATION OF cAMP-RESPONSE ELEMENT-BINDING PROTEIN (CREB). The Journal of biological chemistry 31 25847246
2013 Activation of the PKC pathway stimulates ovarian cancer cell proliferation, migration, and expression of MMP7 and MMP10. Biology of reproduction 31 23843242
2018 MMP7 cleaves remyelination-impairing fibronectin aggregates and its expression is reduced in chronic multiple sclerosis lesions. Glia 30 29600597
2014 Hypomethylation of the MMP7 promoter and increased expression of MMP7 distinguishes the basal-like breast cancer subtype from other triple-negative tumors. Breast cancer research and treatment 29 24847890
2008 HER2-dependent MMP-7 expression is mediated by activated STAT3. Cellular signalling 29 18411043
2019 SULT2B1b promotes epithelial-mesenchymal transition through activation of the β-catenin/MMP7 pathway in hepatocytes. Biochemical and biophysical research communications 28 30658852
2016 MMP7 interacts with ARF in nucleus to potentiate tumor microenvironments for prostate cancer progression in vivo. Oncotarget 28 27356744
2020 miR‑508‑3p suppresses the development of ovarian carcinoma by targeting CCNA2 and MMP7. International journal of oncology 27 32377701
2017 SIPA1 promotes invasion and migration in human oral squamous cell carcinoma by ITGB1 and MMP7. Experimental cell research 27 28237246
2007 Clinicopathological assessment and quantitative estimation of the matrix metalloproteinases MMP-2 and MMP-7 and the inhibitors TIMP-1 and TIMP-2 in colorectal carcinoma tissue samples. Anticancer research 27 17649785
2017 Phospholipase Cδ1 suppresses cell migration and invasion of breast cancer cells by modulating KIF3A-mediated ERK1/2/β- catenin/MMP7 signalling. Oncotarget 26 28423710
2015 MMP-7, MMP-8, and MMP-9 in oral and cutaneous squamous cell carcinomas. Oral surgery, oral medicine, oral pathology and oral radiology 26 25697929
2008 Activin A enhances MMP-7 activity via the transcription factor AP-1 in an esophageal squamous cell carcinoma cell line. International journal of oncology 26 18695873
2010 Matrix metalloproteinase (MMP)-7 in salivary gland cancer. Acta oncologica (Stockholm, Sweden) 24 19929564
2018 A MMP7-sensitive photoclickable biomimetic hydrogel for MSC encapsulation towards engineering human cartilage. Journal of biomedical materials research. Part A 23 29577606
2012 LEF-1 regulates proliferation and MMP-7 transcription in breast cancer cells. Genes to cells : devoted to molecular & cellular mechanisms 23 22686279
2020 SLC12A5 interacts and enhances SOX18 activity to promote bladder urothelial carcinoma progression via upregulating MMP7. Cancer science 22 32449280
2016 Sphingomyelinase D from Loxosceles laeta Venom Induces the Expression of MMP7 in Human Keratinocytes: Contribution to Dermonecrosis. PloS one 22 27078876
2016 Oncogenic targets Mmp7, S100a9, Nppb and Aldh1a3 from transcriptome profiling of FAP and Pirc adenomas are downregulated in response to tumor suppression by Clotam. International journal of cancer 21 27706811
2007 MMP-7 (matrilysin) expression in human brain tumors. Molecular carcinogenesis 21 17219436
2023 Melatonin inhibits chondrosarcoma cell proliferation and metastasis by enhancing miR-520f-3p production and suppressing MMP7 expression. Journal of pineal research 20 37057370
2019 CLEC3A, MMP7, and LCN2 as novel markers for predicting recurrence in resected G1 and G2 pancreatic neuroendocrine tumors. Cancer medicine 20 31129920
2016 MicroRNA-143 inhibits colorectal cancer cell proliferation by targeting MMP7. Minerva medica 20 27827523
2014 Epidermal growth factor induces FoxO1 nuclear exclusion to activate MMP7-mediated metastasis of larynx carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 20 25008564
2022 MMP-7 marks severe pancreatic cancer and alters tumor cell signaling by proteolytic release of ectodomains. Biochemical Society transactions 19 35343563
2017 MMP-10, MMP-7, TIMP-1 and TIMP-2 mRNA expression in esophageal cancer. Acta biochimica Polonica 19 28510611
2014 MMP7 and MMP8 genetic polymorphisms in bladder cancer patients. Central European journal of urology 18 24757528
2013 Expression of CREB in primary pterygium and correlation with cyclin D1, ki-67, MMP7, p53, p63, Survivin and Vimentin. Ophthalmic research 18 23838680
2009 MMP7 expression regulated by endocrine therapy in ERbeta-positive colon cancer cells. Journal of experimental & clinical cancer research : CR 18 19785773
2020 Absence of neurotensin attenuates intestinal dysbiosis and inflammation by maintaining Mmp7/α-defensin axis in diet-induced obese mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 32359121
2014 MiR99a modulates MMP7 and MMP13 to regulate invasiveness of Kaposi's sarcoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 17 25234715
2007 Expression of mRNA MMP-7 and mRNA TIMP-1 in non-small cell lung cancer. Anticancer research 17 17695477
2018 Drastic induction of MMP-7 by cortisol in the human amnion: implications for membrane rupture at parturition. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 30303742
1996 Mapping of the metalloproteinase gene matrilysin (MMP7) to human chromosome 11q21-->q22. Cytogenetics and cell genetics 16 8978768

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