Affinage

MMP14

Matrix metalloproteinase-14 · UniProt P50281

Length
582 aa
Mass
65.9 kDa
Annotated
2026-06-10
100 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MT1-MMP (MMP14) is a cell-surface metalloproteinase that functions as a central pericellular proteolytic hub driving ECM remodeling, cell invasion, and the cleavage of signaling receptors across development, metabolism, immunity, and cancer (PMID:10662785, PMID:19901267, PMID:35768470). As a direct collagenase and matrix-degrading enzyme, it cleaves laminin-5 gamma2 to trigger migration (PMID:10662785), remodels fibronectin while regulating α5β1-integrin endocytosis (PMID:22159414), degrades elastin and decorin (PMID:31278967, PMID:19571574), and is the unique collagenolytic MMP required for mesenchymal stem cell 3D invasion and intravasation (PMID:19901267); it amplifies its own reach by activating latent pro-MMP-2, establishing an MT1-MMP/MMP2/RAC1 motility axis (PMID:19617536, PMID:24387669). This invasive activity depends on highly regulated polarized trafficking to invadopodia and podosomes: β1-integrin/collagen adhesion and the Rab8 GTPase drive exocytosis to invasive structures (PMID:17332756), and a network of trafficking machinery—SNX27/retromer, Protrudin/RAB7/FYCO1 ER-endosome contacts, RAB2A-VPS39, the Bet1 SNARE complex, flotillins, and GRAF2/WDR44/MICAL1 export factors—controls its endocytic recycling and surface delivery (PMID:31820782, PMID:32479595, PMID:27255086, PMID:31519727, PMID:30111578, PMID:32344433). The cytoplasmic tail mediates non-proteolytic functions: it binds the radixin FERM domain to co-localize MT1-MMP with its substrate CD44 on the actin cytoskeleton (PMID:26289026), is phosphorylated on Y573 by LIMK1/2 and on Thr567 via Src-EGFR signaling to govern cortactin-endosome association and invadopodia recycling (PMID:27116935, PMID:32205364), and supports proteolysis-independent invadopodia and podosome assembly through actin-based pushing forces (PMID:31653854, PMID:27069022). Beyond matrix degradation, MT1-MMP acts as a sheddase and receptor regulator: it protects FGFR2 by proteolytically inactivating ADAM9 (PMID:22632802), regulates PDGFRβ signaling in vascular smooth muscle (PMID:15805464), cleaves the insulin receptor, GFRAL, PTH1R, VEGFR1, and meprin β to tune metabolic, growth, and angiogenic signaling (PMID:35768470, PMID:35177851, PMID:36892459, PMID:31117124, PMID:35944080), activates latent TGFβ1 in macrophages to drive endothelial-to-mesenchymal transition and cardiac fibrosis (PMID:33063665), and traffics to the nucleus in macrophages to control inflammatory gene programs via a PI3Kδ/Akt/Mi-2-NuRD cascade independent of its protease activity (PMID:22345520). It is also required for developmental and tissue programs including neural crest EMT (PMID:30079980), ciliogenesis through Notch suppression (PMID:32229724), and neuromuscular junction formation (PMID:32208136). Transcriptionally, MMP14 is induced by Snail1-driven invasion programs and repressed by PROX1 (PMID:19915148, PMID:29934628).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2000 High

    Established MT1-MMP as a direct pericellular matrix protease whose own catalytic activity—not merely its activation of secreted MMPs—drives cell migration.

    Evidence Antisense knockdown, in vitro laminin-5 cleavage, and migration assays with MMP inhibitors across cell lines

    PMID:10662785

    Open questions at the time
    • Did not resolve how the enzyme is spatially delivered to migrating fronts
    • Relative contribution of MMP2 amplification left only partly defined
  2. 2005 High

    Showed MT1-MMP physically partners with a growth-factor receptor (PDGFRβ) to regulate signaling and vascular cell behavior in vivo, expanding its role beyond matrix degradation.

    Evidence Reciprocal Co-IP, gene-targeted knockout mice with retroviral rescue, chemotaxis/proliferation assays

    PMID:15805464

    Open questions at the time
    • Whether PDGFRβ is a direct cleavage substrate vs complex partner not fully separated
    • Catalytic dependence of the signaling effect not defined
  3. 2007 High

    Identified the trafficking logic of invasion—adhesion-triggered, Rab8-dependent polarized exocytosis delivering MT1-MMP to invasive structures.

    Evidence Live imaging, Rab8/Rab11 siRNA, constitutively active Rab8, 3D collagen invasion assays

    PMID:17332756

    Open questions at the time
    • Upstream link from integrin signaling to Rab8 activation unresolved
    • Vesicle tethering/fusion machinery not yet identified
  4. 2009 High

    Placed MT1-MMP as the obligatory, non-redundant effector of multiple invasion and tissue programs (Snail1-driven cancer invasion, MSC collagenolysis/intravasation, glioma-microglia crosstalk, HSC mobilization).

    Evidence siRNA epistasis among collagenolytic MMPs, ectopic rescue, MT1-MMP-deficient mice, in vivo intravasation/mobilization/glioma models, CD44 cleavage

    PMID:19197139 PMID:19571574 PMID:19617536 PMID:19901267 PMID:19915148

    Open questions at the time
    • How secreted MMPs fail to substitute mechanistically not fully explained
    • Cell-type-specific transcriptional control of MMP14 induction incomplete
  5. 2012 High

    Revealed proteolysis-independent functions: MT1-MMP protects FGFR2 by inactivating ADAM9 and translocates to the nucleus to restrain macrophage inflammatory programs via PI3Kδ/Akt/Mi-2-NuRD.

    Evidence Co-IP, Mmp14-/- mice with Adam9 double-KO rescue, nuclear fractionation, pathway dissection, in vivo immune stimulation

    PMID:22345520 PMID:22632802

    Open questions at the time
    • Mechanism of nuclear import of a transmembrane protease unresolved
    • How catalytic and nuclear/non-catalytic pools are partitioned unknown
  6. 2015 High

    Defined the structural basis of cytoplasmic-tail-mediated substrate presentation, with radixin bridging MT1-MMP to CD44 and the actin cytoskeleton.

    Evidence Crystal structure of MT1-MMP tail–radixin FERM complex, Co-IP, co-localization microscopy

    PMID:26289026

    Open questions at the time
    • Whether ERM binding is regulated by tail phosphorylation not tested here
    • Functional consequences for CD44 shedding quantitatively undefined
  7. 2016 High

    Dissected cytoplasmic-tail phosphorylation and actin-anchoring as regulators of invadopodia/podosome assembly and endosomal cortactin association.

    Evidence Co-IP, Y573 site-directed mutagenesis, LIMK1/2 knockdown, TIRF live imaging of podosomes, tail truncation constructs

    PMID:27069022 PMID:27116935

    Open questions at the time
    • Interplay between Y573 and Thr567 phosphorylation not integrated
    • Kinase activation cues incompletely mapped
  8. 2019 High

    Separated mechanical/structural from catalytic roles of MT1-MMP in invadopodia and broadened its substrate repertoire to elastin, TSP1, and VEGFR1.

    Evidence EM ultrastructure and force measurement with inactive mutants; in vitro elastin/TSP1/VEGFR1 cleavage; conditional endothelial KO; exosome assays; MTCBP-1 displacement and Bet1/Protrudin trafficking studies

    PMID:30487181 PMID:31117124 PMID:31278967 PMID:31519727 PMID:31653854 PMID:31793743 PMID:31820782

    Open questions at the time
    • Physiological in vivo relevance of several in vitro cleavages (elastin, VEGFR1) not established
    • How distinct trafficking routes are coordinated at single-cell level unclear
  9. 2020 High

    Consolidated MT1-MMP trafficking machinery and added new developmental/signaling roles—ciliogenesis via Notch, NMJ formation, EndMT via TGFβ1, and metabolic receptor cleavage.

    Evidence SNX27/retromer ITC binding with xenografts, Protrudin/RAB7/FYCO1 imaging, GRAF2/WDR44/MICAL1 export, flotillin endocytosis, conditional KOs (Notch rescue, macrophage TGFβ1/EndMT), Src-EGFR Thr567 phosphorylation

    PMID:30111578 PMID:31820782 PMID:32205364 PMID:32208136 PMID:32229724 PMID:32344433 PMID:32479595 PMID:33063665

    Open questions at the time
    • Whether the many trafficking factors act sequentially or in parallel branches is unresolved
    • Tissue specificity of MT1-MMP receptor cleavage selectivity not fully explained
  10. 2022 High

    Established MT1-MMP as an age- and obesity-activated receptor sheddase controlling systemic metabolism by cleaving the insulin receptor, GFRAL, and meprin β.

    Evidence In vitro cleavage with MS site mapping, KO and tissue-specific conditional KO, liver overexpression, GFRAL-KO epistasis, inhibitor treatment in aged/obese/diabetic mice

    PMID:35177851 PMID:35768470 PMID:35944080

    Open questions at the time
    • Trigger that 'activates' MT1-MMP in ageing/obesity not defined
    • Substrate selectivity determinants among receptors unknown
  11. 2023 High

    Extended receptor-cleavage signaling control to skeletal biology, with MMP14 dampening PTH signaling by cleaving PTH1R in the hypertrophic chondrocyte-derived osteoblast lineage.

    Evidence HC lineage-specific conditional KO, PTH1R cleavage assay, single-cell transcriptomics, in vivo bone phenotype

    PMID:36892459

    Open questions at the time
    • Direct vs indirect cleavage of PTH1R in vivo not fully isolated
    • Generality across other GPCRs untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MT1-MMP's many regulatory inputs—tail phosphorylation, ERM/actin anchoring, and a redundant array of trafficking factors—are integrated to select substrates and direct catalytic versus non-catalytic functions in a given cell context remains unresolved.
  • No unified model linking trafficking branches to specific substrate cleavage events
  • Mechanism switching between protease, sheddase, structural, and nuclear roles undefined
  • In vivo substrate selectivity determinants unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016787 hydrolase activity 4 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005768 endosome 5 GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 3 GO:0005856 cytoskeleton 3 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-9609507 Protein localization 5 R-HSA-1474244 Extracellular matrix organization 4 R-HSA-1266738 Developmental Biology 3 R-HSA-168256 Immune System 2 R-HSA-392499 Metabolism of proteins 2
Partners
ADAM9CD44CDCP1FGFR2PDGFRBRDXSNX27TIMP2
Complex memberships
MT1-MMP/TIMP-2/pro-MMP-2 activation complexMi-2/NuRD-associated nuclear signaling module

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 MT1-MMP directly cleaves the gamma2 subunit of laminin-5, and this proteolytic activity is the primary trigger for cell migration over laminin-5, with MMP2 (activated by MT1-MMP) playing an ancillary amplification role. Antisense oligonucleotide knockdown, gelatin zymography, Western blotting, cell migration assays with MMP inhibitors (BB94, TIMPs), and direct in vitro cleavage assay of laminin-5 by MT1-MMP The Journal of cell biology High 10662785
2005 MT1-MMP associates with PDGFRβ in membrane complexes in vascular smooth muscle cells (VSMCs) and acts as a PDGF-B-selective regulator of PDGFRβ-dependent signal transduction (ERK1/2 and Akt activation), promoting VSMC chemotaxis and proliferation; MT1-MMP-deficient brain tissues show reduced mural cell density and abnormal vessel wall morphology. Gene-targeted MT1-MMP-deficient mice, retroviral rescue with wild-type protease, co-immunoprecipitation of MT1-MMP with PDGFRβ, chemotaxis and proliferation assays, MMP inhibitor treatment Genes & development High 15805464
2007 MT1-MMP polarized exocytosis to invasive structures is triggered by β1 integrin-mediated adhesion to collagen and is regulated by the Rab8 GTPase; MT1-MMP localizes within VSV-G/Rab8-positive vesicles, and constitutively active Rab8 mutants induce MT1-MMP exocytic traffic, collagen degradation and invasion, while Rab8 knockdown inhibits these processes. Live-cell imaging, siRNA knockdown of Rab8 and Rab11, constitutively active Rab8 mutant expression, 3D collagen invasion assays, co-localization studies The EMBO journal High 17332756
2009 Snail1 induces cancer cell basement membrane invasion, angiogenesis, and intravasation via a program that requires MT1-MMP (and MT2-MMP); siRNA silencing of MT1-MMP completely ablates Snail1-driven invasion, and direct expression of MT1-MMP recapitulates the full Snail1 invasion program, which cannot be mimicked by secreted MMPs. siRNA knockdown, ectopic MT1-MMP expression, in vivo intravasation and angiogenesis assays, comparison with secreted MMP family members Proceedings of the National Academy of Sciences of the United States of America High 19915148
2009 MT1-MMP expression and activity in microglia is induced by glioma-released factors via microglial toll-like receptors and the p38 MAPK pathway (MyD88-dependent), and microglial MT1-MMP in turn activates glioma-derived pro-MMP-2 to promote glioma expansion. MT1-MMP-deficient brain tissue ex vivo model, microglia depletion, MyD88 deletion, p38 inhibition, in vivo glioma expansion models Proceedings of the National Academy of Sciences of the United States of America High 19617536
2009 MT1-MMP is required for human mesenchymal stem cell (hMSC) collagenolysis, 3D invasion/intravasation through type I collagen, and MSC differentiation in a 3D-collagen-specific manner; among five collagenolytic MMPs expressed by hMSCs, only MT1-MMP knockdown abrogates these activities. Specific siRNA knockdown of each of five collagenolytic MMPs, 3D invasion assays, intravasation assays, differentiation assays in 3D collagen Blood High 19901267
2009 MT1-MMP and its inhibitor RECK regulate hematopoietic progenitor cell (CD34+) mobilization: G-CSF increases MT1-MMP and decreases RECK expression via PI3K/Akt signaling, elevating MT1-MMP activity; MT1-MMP-mediated cleavage of membrane CD44 reduces CD34+ cell adhesion and promotes egress; MT1-MMP-deficient mouse BM cells show impaired chemotaxis, homing, and G-CSF-induced mobilization. Anti-MT1-MMP antibodies, siRNA, MT1-MMP-deficient mice, chimeric NOD/SCID mouse engraftment, PI3K inhibitors, CD44-deficient mice The Journal of clinical investigation High 19197139
2011 MT1-MMP regulates ECM fibronectin turnover by promoting extracellular cleavage of fibronectin and by regulating α5β1-integrin endocytosis; cells lacking MT1-MMP show reduced fibronectin turnover and endocytosis, and fibronectin polymerization inhibits ECM fibronectin endocytosis by inhibiting α5β1-integrin endocytosis. MT1-MMP-null cells, fibronectin turnover assays, integrin endocytosis assays, inhibitor studies Journal of cell science High 22159414
2012 MT1-MMP forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9, thereby protecting FGFR2 from ADAM9-mediated ectodomain shedding; in Mmp14-/- osteoblasts, ADAM9 is upregulated and FGFR2 is shed, impairing FGF-induced proliferation and signaling; Adam9 depletion completely rescues defective FGFR2 signaling and largely restores calvarial bone growth in Mmp14-/- embryos. Co-immunoprecipitation, Mmp14-/- mice, Adam9 depletion rescue experiments, FGFR2 shedding assays, downstream signaling (proliferation, pERK) measurement Developmental cell High 22632802
2012 MT1-MMP controls macrophage inflammatory gene responses in a protease-independent fashion by trafficking to the nuclear compartment, where it activates a PI3Kδ/Akt/GSK3β signaling cascade that in turn regulates the Mi-2/NuRD nucleosome remodeling complex; MT1-MMP-/- macrophages mount exaggerated chemokine and cytokine responses to immune stimuli. MT1-MMP-/- macrophages, nuclear fractionation, in vitro and in vivo immune stimulation assays, PI3Kδ pathway analysis, Mi-2/NuRD complex analysis Genes & development High 22345520
2014 Atypical PKCι (aPKCι) associates with MT1-MMP-containing late endocytic compartments and phosphorylates cortactin, which regulates cortactin association with dynamin-2 and controls delivery of MT1-MMP from late endosomes to the plasma membrane for matrix degradation and invasion. siRNA silencing of aPKC, co-localization studies, phosphorylation assays, invasion and matrix degradation assays, clinical tissue co-expression analysis Proceedings of the National Academy of Sciences of the United States of America Medium 24753582
2014 TIMP-2 binding to MT1-MMP activates the AKT pathway in a manner independent of MT1-MMP proteolytic activity but requiring the cytoplasmic domain of MT1-MMP and Ras activation; this protects tumor cells from apoptosis induced by serum starvation. MT1-MMP mutants (cytoplasmic domain, catalytic site), AKT phosphorylation assays, apoptosis assays, Ras activation assays PloS one Medium 26331622
2015 MT1-MMP cytoplasmic tail directly binds the FERM domain of radixin (ERM protein); crystal structure shows the central region of the MT1-MMP cytoplasmic tail binds subdomain A of the FERM domain via antiparallel β-β interaction; radixin simultaneously binds both MT1-MMP and CD44, co-localizing MT1-MMP with its substrate CD44 at the cell surface and anchoring them to F-actin. Crystal structure determination, co-immunoprecipitation, binding assays, fluorescence microscopy Genes to cells : devoted to molecular & cellular mechanisms High 26289026
2016 MT1-MMP is a novel substrate/interacting partner of LIMK1 and LIMK2, which phosphorylate tyrosine Y573 in the cytoplasmic domain of MT1-MMP; this phosphorylation influences cortactin association with MT1-MMP-positive endosomes, invadopodia formation, and matrix degradation; LIMK1 controls cortactin-endosome association while LIMK2 controls invadopodia-associated cortactin. Co-immunoprecipitation, phosphorylation assays with Y573 mutant, LIMK1/2 knockdown, invasion and matrix degradation assays in 3D collagen Scientific reports Medium 27116935
2016 MT1-MMP islets in the plasma membrane of primary human macrophages serve as sites of podosome re-emergence; islet formation requires the cytoplasmic tail of MT1-MMP and its ability to bind the subcortical actin cytoskeleton; this structural function of MT1-MMP is independent of its proteolytic activity. TIRF microscopy, siRNA knockdown, MT1-MMP cytoplasmic tail truncation/mutation constructs, live imaging of podosome dynamics The Journal of cell biology High 27069022
2016 RAB2A controls post-endocytic trafficking of MT1-MMP by interacting with VPS39, a component of the late endosomal HOPS complex; RAB2A depletion impairs MT1-MMP proteolytic activity, 3D invasiveness, and matrix remodeling. Functional siRNA screen of human RAB GTPases, Co-IP of RAB2A with VPS39, MT1-MMP activity and invasion assays EMBO reports Medium 27255086
2018 PROX1 transcription factor suppresses MMP14 transcription by binding and suppressing the MMP14 promoter; Prox1 deletion in murine dermal lymphatic vessels increases MMP14 expression; PROX1 ectopic expression reduces MMP14-dependent 3D invasiveness. PROX1 knockdown and overexpression, MMP14 promoter binding assay, in vivo Prox1-conditional deletion, 3D invasion assays Scientific reports Medium 29934628
2018 MMP14 regulates neural crest cell EMT and migration; overexpression leads to premature NCC migration and decreased cadherin expression; knockdown results in reduced migration and increased cadherin expression; MMP14 is required in NCCs (not surrounding mesenchyme), while MMP2 (activated by MMP14) is required in the surrounding mesenchyme. Xenopus overexpression and morpholino knockdown, cell transplantation experiments, in vitro explant culture, cadherin expression analysis Developmental dynamics Medium 30079980
2019 MT1-MMP directs invadopodia assembly independent of its proteolytic activity; its matrix-degradative activity is required to widen matrix pores; actin polymerization produces pushing forces that repel collagen fibers; these forces require Arp2/3-based actin network assembly at the concave side of curved invadopodia. Electron microscopy ultrastructural analysis, live-cell imaging, force measurement, proteolytically inactive MT1-MMP mutants, theoretical mechanical modeling Nature communications High 31653854
2019 MMP14-containing exosomes produced by corneal fibroblasts cleave VEGFR1 (but not VEGFR2), and this MMP14-dependent VEGFR1 cleavage promotes VEGFA-induced endothelial cell migration and proliferation. Exosome isolation by ultracentrifugation, in vitro proteolysis of recombinant VEGFR1/R2, MMP14-exon4 deficient cells, pan-MMP inhibitor, endothelial cell migration (Boyden chamber) and BrdU proliferation assays Investigative ophthalmology & visual science Medium 31117124
2019 MT1-MMP activity in endothelial cells is required for vasodilation and intussusceptive angiogenesis (IA), as well as for nitric oxide production, via cleavage of thrombospondin-1 (TSP1); the C-terminal fragment of TSP1 generated by MT1-MMP binds CD47/αvβ3 integrin to promote IA. Endothelial cell-specific MT1-MMP conditional KO mice (MT1iΔEC), intravital microscopy, lentiviral rescue, in vitro endothelial cell culture, TSP1 cleavage assay EMBO molecular medicine High 31793743
2019 MT1-MMP cleaves tropoelastin and mature skin elastin, preferring small/medium hydrophobic residues (Gly, Ala, Leu, Val) at the P1' cleavage site; cleavage of mature elastin releases bioactive elastin peptides. In vitro digestion of recombinant human tropoelastin and human skin elastin, mass spectrometry-based cleavage site analysis, molecular docking Biochimie Medium 31278967
2019 MTCBP-1 (MT1-MMP cytoplasmic tail binding protein 1) interacts with the MT1-MMP cytoplasmic tail, displaces MT1-MMP from invadopodia, attenuates invadopodia number and function, and reduces matrix degradation and metastasis; MTCBP-1 and MT1-MMP expression are inversely correlated in pancreatic tumors. Co-immunoprecipitation, siRNA/overexpression studies, invadopodia assays, in vitro invasion assays, in vivo xenograft metastasis models The Journal of cell biology High 30487181
2019 MT1-MMP recruits the ER-Golgi SNARE Bet1 to MT1-MMP-positive endosomes, where Bet1 forms a novel SNARE complex with syntaxin 4 and endosomal SNAREs to promote MT1-MMP trafficking to the cell surface/invadopodia; MT1-MMP also uses Bet1 for its export from raft-like ER structures. Co-immunoprecipitation, subcellular fractionation, SNARE complex analysis, Bet1 knockdown, MT1-MMP surface delivery assays, invasion assays The Journal of cell biology Medium 31519727
2020 Protrudin (ER protein) forms contact sites with MT1-MMP-positive RAB7/FYCO1-containing endosomes and promotes anterograde translocation and exocytosis of MT1-MMP to invadopodia; depletion of RAB7, FYCO1, or Protrudin inhibits MT1-MMP-dependent ECM degradation and invasion; Synaptotagmin VII mediates MT1-MMP exocytosis at invadopodia. siRNA depletion, live-cell imaging, MT1-MMP exocytosis assays, ECM degradation assays, invasion assays, Protrudin overexpression The Journal of cell biology High 32479595
2020 Macrophage MT1-MMP activates latent TGFβ1, leading to paracrine SMAD2-mediated signaling in endothelial cells and endothelial-to-mesenchymal transition (EndMT) contributing to cardiac fibrosis post-MI; macrophage-specific Mmp14 conditional KO attenuates post-MI cardiac dysfunction, fibrosis, and reduces EndMT. Macrophage-specific Mmp14 conditional KO (Mmp14f/f:Lyz2-Cre), co-culture of Mmp14-deficient macrophages with endothelial cells, TGFβ1 activation assay, SMAD2 signaling measurement, cardiac function assessment eLife High 33063665
2020 SNX27 and retromer directly interact with MT1-MMP (demonstrated by ITC-based binding studies) and selectively recycle MT1-MMP (but not MT2-MMP) to invadopodia to enable matrix invasion; SNX27 depletion reduces MT1-MMP-mediated matrix degradation and prolongs survival in SCID mouse xenograft models. ITC (isothermal titration calorimetry) binding assays, retromer/SNX27 depletion, matrix degradation assays, invadopodia assays, xenograft models The Journal of cell biology High 31820782
2020 β1 integrin activation induces phosphorylation of MT1-MMP on Thr567 via a Src-EGFR signaling pathway, promoting MT1-MMP internalization, recycling to invadopodia, and increased cellular invasiveness and invadopodium formation. β1 integrin-activating antibody, Src and EGFR phosphorylation assays, MT1-MMP Thr567 phosphorylation measurement, invasion and invadopodium formation assays Journal of cell science Medium 32205364
2020 MT1-MMP is required for ciliogenesis and ependymal cell maturation through suppression of Notch signaling; MT1-MMP-deficient mice develop hydrocephalus with reduced/disorganized motile cilia; inhibition of Notch signaling by γ-secretase inhibitor restores ciliogenesis in Mmp14-/- ependymal cells. Mmp14-/- mice, Notch signaling pathway analysis, γ-secretase inhibitor rescue, in situ hybridization, ciliary morphogenesis assessment JCI insight High 32229724
2020 MT1-MMP is required for podosome-like structure (PLS)-directed trafficking and surface insertion at AChR clusters to enable focal ECM degradation during NMJ formation; MT1-MMP plays a role in recruitment of aneural AChR clusters for postsynaptic specialization assembly; MT1-MMP-/- embryos exhibit structural NMJ defects. MT1-MMP-/- mice, live imaging of MT1-MMP trafficking, ECM degradation assays at AChR clusters, microtubule-capturing assay eLife Medium 32208136
2022 Ageing-activated MT1-MMP cleaves the insulin receptor to suppress insulin signaling; MT1-MMP inhibition restores insulin receptor expression and improves insulin sensitivity in aged mice; MT1-MMP overexpression in the liver reduces insulin receptor levels and impairs hepatic insulin sensitivity in young mice. MT1-MMP-/- mice, MT1-MMP liver overexpression, insulin receptor cleavage assays, insulin signaling measurement, aged mouse models, diabetic mouse models, MT1-MMP inhibitor treatment Nature communications High 35768470
2022 Obesity-induced MT1-MMP activation proteolytically inactivates GFRAL (GDF15 receptor) in neurons, suppressing GDF15-GFRAL signaling and attenuating anorectic effects; neuron-specific ablation of MT1-MMP in GFRAL+ cells restores GFRAL expression and reduces weight gain/food intake in obese mice. GFRAL+ neuron-specific MT1-MMP conditional KO, GFRAL cleavage assay, GDF15 signaling measurement, body weight and food intake measurement, GFRAL-deficient epistasis experiments Nature metabolism High 35177851
2022 MT1-MMP sheds meprin β from the plasma membrane, releasing soluble meprin β; mass spectrometry analysis reveals cleavage occurs between Pro602 and Ser603 (N-terminal of the EGF-like domain); vice versa, meprin β also sheds MT1-MMP, indicating bidirectional regulation. Cell-based shedding assays, mass spectrometry-based cleavage site analysis, inactive MT1-MMP mutants The FEBS journal Medium 35944080
2023 MMP14 cleaves the extracellular domain of PTH1R (parathyroid hormone receptor 1) in the hypertrophic chondrocyte-derived osteoblast lineage, dampening PTH signaling; HC lineage-specific Mmp14 KO (Mmp14ΔHC) results in enhanced PTH signaling and increased bone production. HC lineage-specific Mmp14 conditional KO, PTH1R cleavage assay, single-cell transcriptomics, PTH signaling measurement, bone formation assays eLife High 36892459
2009 MT1-MMP cleaves decorin in corneal fibroblasts in a time- and concentration-dependent manner in vitro; MT1-MMP-deficient corneal cell lysates show diminished decorin cleavage, and MT1-MMP knockin restores it; MT1-MMP-mediated decorin cleavage reduces the inhibitory effects of decorin on aortic ring tube formation. Western blotting for decorin degradation, MT1-MMP-deficient corneal cells, knockin rescue, aortic ring tube formation assay, in vivo corneal micropocket bFGF model Journal of vascular research Medium 19571574
2013 MT1-MMP interacts with tetraspanins (CD9, CD37, CD53, CD63, CD81, CD82) and EWI-2 via its hemopexin domain in the endoplasmic reticulum; this interaction is independent of O-glycosylation; different tetraspanins differentially affect MT1-MMP cell surface localization, pro-MMP-2 activation, and collagen invasion capacity. Yeast two-hybrid screen, co-immunoprecipitation, MT1-MMP truncation/mutant constructs, subcellular localization analysis, pro-MMP-2 activation assay, invasion assay The international journal of biochemistry & cell biology Medium 23500527
2018 Flotillin-1/2 upregulation promotes RAB5-dependent MT1-MMP endocytosis and delivery to RAB7-positive endolysosomal reservoirs; flotillin knockdown reduces MT1-MMP accumulation in endolysosomes, subsequent exocytosis at invadopodia, ECM degradation, and cell invasion. Flotillin siRNA knockdown, flotillin overexpression, RAB5/RAB7 co-localization, MT1-MMP endocytosis and exocytosis assays, ECM degradation and invasion assays Journal of cell science Medium 30111578
2013 CDCP1 co-immunoprecipitates with MT1-MMP and co-localizes with MT1-MMP at caveolin-1-containing vesicular structures and lipid rafts; CDCP1 knockdown markedly inhibits MT1-MMP accumulation at invadopodia, MT1-MMP-dependent ECM degradation, and Matrigel invasion. Co-immunoprecipitation, siRNA knockdown, immunofluorescence co-localization, ECM degradation assay, Matrigel invasion assay Molecular cancer research : MCR Medium 23439492
2020 GRAF2 and WDR44 are essential for the export of neosynthesized MT1-MMP (along with E-cadherin and CFTR ΔF508) via a Rab8/Rab10/Rab11-dependent exocytic pathway; MICAL1 links GRAF2 to Rab8a/b and Rab10, and WDR44 binds Rab11; dominant-negative mutants of GRAF1/2, WDR44, and MICAL1 interfere with MT1-MMP exocytosis. siRNA depletion, dominant-negative mutant expression, co-localization studies, MT1-MMP surface delivery assays The Journal of cell biology Medium 32344433
2014 MT1-MMP modulates melanoma cell invasion by activating its target MMP2, and MMP2 activation by MT1-MMP is required to sustain RAC1 activity and promote MT1-MMP-dependent cell motility, establishing a MT1-MMP/MMP2/RAC1 signaling axis. MT1-MMP depletion, MMP2 activation assays, RAC1 activity assay, orthotopic mouse melanoma metastasis model Pigment cell & melanoma research Medium 24387669

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Role of cell surface metalloprotease MT1-MMP in epithelial cell migration over laminin-5. The Journal of cell biology 529 10662785
2006 MT1-MMP: a potent modifier of pericellular microenvironment. Journal of cellular physiology 413 15920734
2009 Matrix invasion by tumour cells: a focus on MT1-MMP trafficking to invadopodia. Journal of cell science 385 19692588
2009 Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion. Proceedings of the National Academy of Sciences of the United States of America 317 19617536
2007 MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway. The EMBO journal 209 17332756
2016 Cellular and Molecular Mechanisms of MT1-MMP-Dependent Cancer Cell Invasion. Annual review of cell and developmental biology 193 27501444
2003 MT1-MMP and MMP-7 in invasion and metastasis of human cancers. Cancer metastasis reviews 188 12784993
2009 Induction of a MT1-MMP and MT2-MMP-dependent basement membrane transmigration program in cancer cells by Snail1. Proceedings of the National Academy of Sciences of the United States of America 181 19915148
2004 MT1-MMP: a tethered collagenase. Journal of cellular physiology 144 15137053
2006 MT1-MMP: a key regulator of cell migration in tissue. IUBMB life 140 17050376
2006 MT1-MMP: universal or particular player in angiogenesis? Cancer metastasis reviews 106 16680574
2005 An MT1-MMP-PDGF receptor-beta axis regulates mural cell investment of the microvasculature. Genes & development 106 15805464
2011 MT1-MMP regulates the turnover and endocytosis of extracellular matrix fibronectin. Journal of cell science 105 22159414
2001 Expression of MMP2, MMP9, MT1-MMP, TIMP1, and TIMP2 mRNA in valvular lesions of the heart. The Journal of pathology 104 11400152
2019 MT1-MMP directs force-producing proteolytic contacts that drive tumor cell invasion. Nature communications 90 31653854
2019 MT1-MMP-dependent cell migration: proteolytic and non-proteolytic mechanisms. Biochemical Society transactions 89 31064864
1997 Analysis of MT1-MMP and MMP2 expression in human gastric cancers. International journal of cancer 86 9221811
2009 MT1-MMP and RECK are involved in human CD34+ progenitor cell retention, egress, and mobilization. The Journal of clinical investigation 85 19197139
2012 MT1-MMP regulates the PI3Kδ·Mi-2/NuRD-dependent control of macrophage immune function. Genes & development 82 22345520
2016 RAB2A controls MT1-MMP endocytic and E-cadherin polarized Golgi trafficking to promote invasive breast cancer programs. EMBO reports 81 27255086
2016 Extracellular Matrix Proteolysis by MT1-MMP Contributes to Influenza-Related Tissue Damage and Mortality. Cell host & microbe 80 27736644
2015 CD44 regulates pancreatic cancer invasion through MT1-MMP. Molecular cancer research : MCR 77 25566991
2014 Control of MT1-MMP transport by atypical PKC during breast-cancer progression. Proceedings of the National Academy of Sciences of the United States of America 76 24753582
2020 Macrophages promote endothelial-to-mesenchymal transition via MT1-MMP/TGFβ1 after myocardial infarction. eLife 73 33063665
2019 MMP14 in Sarcoma: A Regulator of Tumor Microenvironment Communication in Connective Tissues. Cells 71 31466240
2009 MT1-MMP controls human mesenchymal stem cell trafficking and differentiation. Blood 71 19901267
2020 circPTCH1 promotes invasion and metastasis in renal cell carcinoma via regulating miR-485-5p/MMP14 axis. Theranostics 70 32929380
2012 MT1-MMP inactivates ADAM9 to regulate FGFR2 signaling and calvarial osteogenesis. Developmental cell 70 22632802
2004 MT1-MMP: an enzyme with multidimensional regulation. Trends in biochemical sciences 69 15276180
2014 Monitoring and Inhibiting MT1-MMP during Cancer Initiation and Progression. Cancers 66 24549119
2016 LIMK Regulates Tumor-Cell Invasion and Matrix Degradation Through Tyrosine Phosphorylation of MT1-MMP. Scientific reports 63 27116935
2005 Regulation of TIMP-2, MT1-MMP, and MMP-2 expression during C2C12 differentiation. Muscle & nerve 56 16003733
2014 MT1-MMP modulates melanoma cell dissemination and metastasis through activation of MMP2 and RAC1. Pigment cell & melanoma research 55 24387669
2014 Relationship of MMP-14 and TIMP-3 expression with macrophage activation and human atherosclerotic plaque vulnerability. Mediators of inflammation 55 25301980
2006 Role of metalloproteinases MMP-9 and MT1-MMP in CXCL12-promoted myeloma cell invasion across basement membranes. The Journal of pathology 55 16278822
2022 Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu. International journal of molecular sciences 53 36076910
2014 The emerging role of MMP14 in brain tumorigenesis and future therapeutics. Biochimica et biophysica acta 52 24657728
2011 Secretory and endo/exocytic trafficking in invadopodia formation: the MT1-MMP paradigm. European journal of cell biology 52 20605060
2009 MT1-MMP-mediated cleavage of decorin in corneal angiogenesis. Journal of vascular research 51 19571574
2020 Protrudin-mediated ER-endosome contact sites promote MT1-MMP exocytosis and cell invasion. The Journal of cell biology 50 32479595
2016 Metalloproteinase MT1-MMP islets act as memory devices for podosome reemergence. The Journal of cell biology 50 27069022
2015 TIMP-2 Interaction with MT1-MMP Activates the AKT Pathway and Protects Tumor Cells from Apoptosis. PloS one 49 26331622
2015 MMP-14 in skeletal muscle repair. Journal of muscle research and cell motility 44 26025393
2018 TGF-β-induced NKILA inhibits ESCC cell migration and invasion through NF-κB/MMP14 signaling. Journal of molecular medicine (Berlin, Germany) 42 29379981
2020 SNX27-retromer assembly recycles MT1-MMP to invadopodia and promotes breast cancer metastasis. The Journal of cell biology 40 31820782
2010 YB-1 alters MT1-MMP trafficking and stimulates MCF-7 breast tumor invasion and metastasis. Biochemical and biophysical research communications 40 20599698
2010 MT1-MMP and integrins: Hand-to-hand in cell communication. BioFactors (Oxford, England) 40 20818710
2008 p190B RhoGAP regulates endothelial-cell-associated proteolysis through MT1-MMP and MMP2. Journal of cell science 40 18505793
2022 Regulation of age-associated insulin resistance by MT1-MMP-mediated cleavage of insulin receptor. Nature communications 39 35768470
2013 The tetraspanin network modulates MT1-MMP cell surface trafficking. The international journal of biochemistry & cell biology 38 23500527
2012 MMP-14 and MMP-2 are key metalloproteases in Dupuytren's disease fibroblast-mediated contraction. Biochimica et biophysica acta 38 22342364
2019 Endothelial MT1-MMP targeting limits intussusceptive angiogenesis and colitis via TSP1/nitric oxide axis. EMBO molecular medicine 37 31793743
2018 PROX1 is a transcriptional regulator of MMP14. Scientific reports 36 29934628
1997 Co-ordinated expression of MMP-2 and its putative activator, MT1-MMP, in human placentation. Molecular human reproduction 36 9294857
2018 MMP14 Regulates Cranial Neural Crest Epithelial-to-Mesenchymal Transition and Migration. Developmental dynamics : an official publication of the American Association of Anatomists 35 30079980
2018 MT1-MMP targeting to endolysosomes is mediated by upregulation of flotillins. Journal of cell science 35 30111578
2008 Endo180 expression with cofunctional partners MT1-MMP and uPAR-uPA is correlated with prostate cancer progression. European journal of cancer (Oxford, England : 1990) 35 19112015
2016 MMP-14 and CD44 in Epithelial-to-Mesenchymal Transition (EMT) in ovarian cancer. Journal of ovarian research 34 27590006
2007 Phagocytosis of collagen by fibroblasts and invasive cancer cells is mediated by MT1-MMP. Biochemical Society transactions 34 17635128
2015 Expression of MMP14 in invasive pituitary adenomas: relationship to invasion and angiogenesis. International journal of clinical and experimental pathology 33 26097538
2020 GRAF2, WDR44, and MICAL1 mediate Rab8/10/11-dependent export of E-cadherin, MMP14, and CFTR ΔF508. The Journal of cell biology 32 32344433
2018 Pancreatic tumor cell metastasis is restricted by MT1-MMP binding protein MTCBP-1. The Journal of cell biology 32 30487181
2023 MT1-MMP as a Key Regulator of Metastasis. Cells 31 37681919
2022 Body weight regulation via MT1-MMP-mediated cleavage of GFRAL. Nature metabolism 31 35177851
2019 MMP14-Containing Exosomes Cleave VEGFR1 and Promote VEGFA-Induced Migration and Proliferation of Vascular Endothelial Cells. Investigative ophthalmology & visual science 31 31117124
2013 CDCP1 regulates the function of MT1-MMP and invadopodia-mediated invasion of cancer cells. Molecular cancer research : MCR 31 23439492
2008 Role of MT1-MMP in the osteogenic differentiation. Bone 31 19027888
2018 High serum MMP-14 predicts worse survival in gastric cancer. PloS one 30 30532247
2015 KIF1B promotes glioma migration and invasion via cell surface localization of MT1-MMP. Oncology reports 30 26576027
2006 Immunohistochemical detection of MT1-MMP, RECK, and EMMPRIN in ameloblastic tumors. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 30 16762015
2021 The role of MMP-14 in ovarian cancer: a systematic review. Journal of ovarian research 28 34344453
2016 Multiple essential MT1-MMP functions in tooth root formation, dentinogenesis, and tooth eruption. Matrix biology : journal of the International Society for Matrix Biology 28 26780723
1999 Expression of gelatinase A and its activator MT1-MMP in the inflammatory periprosthetic response to polyethylene. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 27 9933484
2020 β1 integrin-mediated signaling regulates MT1-MMP phosphorylation to promote tumor cell invasion. Journal of cell science 26 32205364
2020 MT1-MMP deficiency leads to defective ependymal cell maturation, impaired ciliogenesis, and hydrocephalus. JCI insight 26 32229724
2008 MT1-MMP regulates urothelial cell invasion via transcriptional regulation of Dickkopf-3. British journal of cancer 26 18665176
2020 Site-directed MT1-MMP trafficking and surface insertion regulate AChR clustering and remodeling at developing NMJs. eLife 25 32208136
2018 MMP14 empowers tumor-initiating breast cancer cells under hypoxic nutrient-depleted conditions. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25 30521382
2015 MT1-MMP recognition by ERM proteins and its implication in CD44 shedding. Genes to cells : devoted to molecular & cellular mechanisms 25 26289026
2023 Bone sialoprotein promotes lung cancer osteolytic bone metastasis via MMP14-dependent mechanisms. Biochemical pharmacology 23 37028462
2012 Site-specific cellular functions of MT1-MMP. European journal of cell biology 23 22939226
2023 MMP14 cleaves PTH1R in the chondrocyte-derived osteoblast lineage, curbing signaling intensity for proper bone anabolism. eLife 22 36892459
2019 TMZ regulates GBM stemness via MMP14-DLL4-Notch3 pathway. International journal of cancer 22 31443114
2016 Tip60 regulates MT1-MMP transcription and invasion of glioblastoma cells through NF-κB pathway. Clinical & experimental metastasis 22 26464124
2015 RABGTPases in MT1-MMP trafficking and cell invasion: Physiology versus pathology. Small GTPases 22 26107110
2019 MMP-14 degrades tropoelastin and elastin. Biochimie 20 31278967
2010 Involvement of MT1-MMP and TIMP-2 in human periodontal disease. Oral diseases 20 20233321
2010 MT1-MMP-mediated basement membrane remodeling modulates renal development. Experimental cell research 20 20727881
2022 MT1-MMP and ADAM10/17 exhibit a remarkable overlap of shedding properties. The FEBS journal 19 35944080
2019 MT1-MMP recruits the ER-Golgi SNARE Bet1 for efficient MT1-MMP transport to the plasma membrane. The Journal of cell biology 19 31519727
2011 MT1-MMP and RECK: opposite and essential roles in hematopoietic stem and progenitor cell retention and migration. Journal of molecular medicine (Berlin, Germany) 19 21842347
2024 The interplay of Cxcl10+/Mmp14+ monocytes and Ccl3+ neutrophils proactively mediates silica-induced pulmonary fibrosis. Journal of hazardous materials 18 38335607
2023 Starvation-inactivated MTOR triggers cell migration via a ULK1-SH3PXD2A/TKS5-MMP14 pathway in ovarian carcinoma. Autophagy 18 37505094
2019 Metalloproteinase 14 (MMP-14) and hsa-miR-410-3p expression in human inflamed dental pulp and odontoblasts. Histochemistry and cell biology 18 31486923
2012 MT1-MMP modulates bFGF-induced VEGF-A expression in corneal fibroblasts. Protein and peptide letters 18 22670674
2021 Loss of MT1-MMP in Alveolar Epithelial Cells Exacerbates Pulmonary Fibrosis. International journal of molecular sciences 17 33805743
2021 Fibroblast MMP14-Dependent Collagen Processing Is Necessary for Melanoma Growth. Cancers 16 33924099
2020 Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis. Scientific reports 16 33154487
2012 Angiostatin inhibits endothelial MMP-2 and MMP-14 expression: a hypoxia specific mechanism of action. Vascular pharmacology 16 23220260
2012 When MT1-MMP meets ADAMs. Cell cycle (Georgetown, Tex.) 14 22801544

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