Genomes and Genes
Gene Symbol: Mmp14
Description: matrix metallopeptidase 14 (membrane-inserted)
Alias: AI325305, MMP-X1, MT-MMP-1, MT1-MMP, sabe, matrix metalloproteinase-14, Membrane type 1-MMP, matrix metalloproteinase 14 (membrane-inserted), membrane-type-1 matrix metalloproteinase, type 1 matrix metalloprotease 14
- Kheradmand F, Rishi K, Werb Z. Signaling through the EGF receptor controls lung morphogenesis in part by regulating MT1-MMP-mediated activation of gelatinase A/MMP2. J Cell Sci. 2002;115:839-48 pubmed..Egfr(-/-) mice had low expression of MT1-MMP/MMP14, which is a potent activator of gelatinase A/MMP2, in their lungs...
- Holmbeck K, Bianco P, Caterina J, Yamada S, Kromer M, Kuznetsov S, et al. MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell. 1999;99:81-92 pubmed
- Zhou Z, Apte S, Soininen R, Cao R, Baaklini G, Rauser R, et al. Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I. Proc Natl Acad Sci U S A. 2000;97:4052-7 pubmed..In tissues from null mice, activation of latent matrix metalloproteinase 2 was deficient, suggesting that MT1-MMP is essential for its activation in vivo. ..
- Gkantidis N, Katsaros C, Chiquet M. Detection of gelatinolytic activity in developing basement membranes of the mouse embryo head by combining sensitive in situ zymography with immunolabeling. Histochem Cell Biol. 2012;138:557-71 pubmed publisher..Thus, this sensitive method allows to associate, with high spatial resolution, gelatinolytic activity with epithelial morphogenesis in the embryo...
- Sabeh F, Li X, Saunders T, Rowe R, Weiss S. Secreted versus membrane-anchored collagenases: relative roles in fibroblast-dependent collagenolysis and invasion. J Biol Chem. 2009;284:23001-11 pubmed publisher..Herein, we use fibroblasts isolated from Mmp13(-/-), Mmp8(-/-), Mmp2(-/-), Mmp9(-/-), Mmp14(-/-) and Mmp16(-/-) mice to define the functional roles for secreted and membrane-anchored collagenases during ..
- Chun T, Sabeh F, Ota I, Murphy H, McDonagh K, Holmbeck K, et al. MT1-MMP-dependent neovessel formation within the confines of the three-dimensional extracellular matrix. J Cell Biol. 2004;167:757-67 pubmed
- Oh J, Takahashi R, Adachi E, Kondo S, Kuratomi S, Noma A, et al. Mutations in two matrix metalloproteinase genes, MMP-2 and MT1-MMP, are synthetic lethal in mice. Oncogene. 2004;23:5041-8 pubmed..In the absence of MMP-2 and MT1-MMP, myoblast fusion in vitro is also significantly retarded. These findings suggest functional overlap in mice between the two MMPs with distinct molecular natures. ..
- Currie J, Fortier S, Sina A, Galipeau J, Cao J, Annabi B. MT1-MMP down-regulates the glucose 6-phosphate transporter expression in marrow stromal cells: a molecular link between pro-MMP-2 activation, chemotaxis, and cell survival. J Biol Chem. 2007;282:8142-9 pubmed..This may lead to optimized clinical applications that use BMSC as a platform for the systemic delivery of therapeutic or anti-cancer recombinant proteins in vivo. ..
- Yana I, Sagara H, Takaki S, Takatsu K, Nakamura K, Nakao K, et al. Crosstalk between neovessels and mural cells directs the site-specific expression of MT1-MMP to endothelial tip cells. J Cell Sci. 2007;120:1607-14 pubmedThe membrane-anchored matrix metalloproteinase MT1-MMP (also known as Mmp14) plays a key role in the angiogenic process, but the mechanisms underlying its spatiotemporal regulation in the in vivo setting have not been defined...
- Sakamoto T, Seiki M. A membrane protease regulates energy production in macrophages by activating hypoxia-inducible factor-1 via a non-proteolytic mechanism. J Biol Chem. 2010;285:29951-64 pubmed publisher..In this study, we found that macrophages lacking membrane type 1 matrix metalloproteinase (MT1-MMP/MMP-14), a potent invasion-promoting protease, exhibited considerably lower ATP levels ..
- Blavier L, Lazaryev A, Groffen J, Heisterkamp N, DeClerck Y, Kaartinen V. TGF-beta3-induced palatogenesis requires matrix metalloproteinases. Mol Biol Cell. 2001;12:1457-66 pubmed..Our observations indicate for the first time that the proteolytic degradation of the ECM by MMPs is a necessary step for palatal fusion. ..
- Chun T, Hotary K, Sabeh F, Saltiel A, Allen E, Weiss S. A pericellular collagenase directs the 3-dimensional development of white adipose tissue. Cell. 2006;125:577-91 pubmed..Hence, MT1-MMP acts as a 3-D-specific adipogenic factor that directs the dynamic adipocyte-ECM interactions critical to WAT development. ..
- Hotary K, Yana I, Sabeh F, Li X, Holmbeck K, Birkedal Hansen H, et al. Matrix metalloproteinases (MMPs) regulate fibrin-invasive activity via MT1-MMP-dependent and -independent processes. J Exp Med. 2002;195:295-308 pubmed..Given the widespread distribution of MT1-, 2-, and 3-MMP in normal and neoplastic cells, these data identify a subset of membrane-anchored MMPs that operate in an autonomous fashion to drive fibrin-invasive activity. ..
- Robbins J, McGuire P, Wehrle Haller B, Rogers S. Diminished matrix metalloproteinase 2 (MMP-2) in ectomesenchyme-derived tissues of the Patch mutant mouse: regulation of MMP-2 by PDGF and effects on mesenchymal cell migration. Dev Biol. 1999;212:255-63 pubmed
- Holmbeck K, Bianco P, Pidoux I, Inoue S, Billinghurst R, Wu W, et al. The metalloproteinase MT1-MMP is required for normal development and maintenance of osteocyte processes in bone. J Cell Sci. 2005;118:147-56 pubmed..Osteocytogenesis is thus an active invasive process requiring cleavage of collagen for maintenance of the osteocyte phenotype. ..
- Feng M, Cai X, Zhang W, Liu X, Chen L, Zhang Y, et al. Interleukin-6 enhances matrix metalloproteinase-14 expression via the RAF-mitogen-activated protein kinase kinase-extracellular signal-regulated kinase 1/2-activator protein-1 pathway. Clin Exp Pharmacol Physiol. 2010;37:162-6 pubmed publisher..4. These findings suggest a novel molecular pathway for inflammation-associated ECM dysregulation, which may account for atherosclerotic plaque rupture. ..
- Golubkov V, Chekanov A, Doxsey S, Strongin A. Centrosomal pericentrin is a direct cleavage target of membrane type-1 matrix metalloproteinase in humans but not in mice: potential implications for tumorigenesis. J Biol Chem. 2005;280:42237-41 pubmed..Taken together, our results confirm that MT1-MMP cleaves pericentrin-2 in humans but not in mice and that mouse models of cancer probably cannot be used to critically examine MT1-MMP functionality. ..
- Nishida C, Kusubata K, Tashiro Y, Gritli I, Sato A, Ohki Koizumi M, et al. MT1-MMP plays a critical role in hematopoiesis by regulating HIF-mediated chemokine/cytokine gene transcription within niche cells. Blood. 2012;119:5405-16 pubmed publisher..Thus, MT1-MMP in niche cells regulates postnatal hematopoiesis, by modulating hematopoietic HIF-dependent niche factors that are critical for terminal differentiation and migration. ..
- Rowe R, Keena D, Sabeh F, Willis A, Weiss S. Pulmonary fibroblasts mobilize the membrane-tethered matrix metalloprotease, MT1-MMP, to destructively remodel and invade interstitial type I collagen barriers. Am J Physiol Lung Cell Mol Physiol. 2011;301:L683-92 pubmed publisher..Together, these findings demonstrate that MT1-MMP serves as a key effector of type I collagenolytic activity in pulmonary fibroblasts and earmark this pericellular collagenase as a potential target for therapeutic intervention. ..
- Jáuregui E, Akil O, Acevedo C, Hall Glenn F, Tsai B, Bale H, et al. Parallel mechanisms suppress cochlear bone remodeling to protect hearing. Bone. 2016;89:7-15 pubmed publisher..Understanding the cellular and molecular mechanisms that confer site-specific control of bone remodeling has the potential to elucidate new pathways that are deregulated in skeletal disease. ..
- Wang X, Inoue S, Gu J, Miyoshi E, Noda K, Li W, et al. Dysregulation of TGF-beta1 receptor activation leads to abnormal lung development and emphysema-like phenotype in core fucose-deficient mice. Proc Natl Acad Sci U S A. 2005;102:15791-6 pubmed..We propose that the lack of core fucosylation of TGF-beta1 receptors is crucial for a developmental and progressive/destructive emphysema, suggesting that perturbation of this function could underlie certain cases of human emphysema. ..
- Muhs B, Plitas G, Delgado Y, Ianus I, Shaw J, Adelman M, et al. Temporal expression and activation of matrix metalloproteinases-2, -9, and membrane type 1-matrix metalloproteinase following acute hindlimb ischemia. J Surg Res. 2003;111:8-15 pubmed..Primed PMNs, along with constitutively expressed MT1-MMP, may activate MMPs-2 and -9 and enable tissue remodeling essential for limb revascularization and angiogenesis. ..
- Ohtake Y, Tojo H, Seiki M. Multifunctional roles of MT1-MMP in myofiber formation and morphostatic maintenance of skeletal muscle. J Cell Sci. 2006;119:3822-32 pubmed..Thus, MT1-MMP is a new multilateral regulator for muscle differentiation and maintenance through processing of stage-specific distinct ECM substrates. ..
- Itoh Y. Membrane-type matrix metalloproteinases: Their functions and regulations. Matrix Biol. 2015;44-46:207-23 pubmed publisher..Further investigations of MT-MMPs are likely to reveal novel pathophysiological mechanisms and potential therapeutic strategies for different diseases in the future. ..
- Chang J, Javier J, Chang G, Oliveira H, Azar D. Functional characterization of neostatins, the MMP-derived, enzymatic cleavage products of type XVIII collagen. FEBS Lett. 2005;579:3601-6 pubmed..These results provide supportive evidence of the possible anti-angiogenic effect of neostatins. ..
- Sakamoto T, Seiki M. Cytoplasmic tail of MT1-MMP regulates macrophage motility independently from its protease activity. Genes Cells. 2009;14:617-26 pubmed publisher..Thus, we have demonstrated that MT1-MMP regulates macrophages via its invasion-promoting protease activity as well as its CP-dependent non-proteolytic activity to boost cell migration. ..
- Atkinson J, Toennies H, Holmbeck K, Senior R. Membrane type 1 matrix metalloproteinase is necessary for distal airway epithelial repair and keratinocyte growth factor receptor expression after acute injury. Am J Physiol Lung Cell Mol Physiol. 2007;293:L600-10 pubmedb>Membrane type 1 matrix metalloproteinase (MT1-MMP) is a protease produced by airway epithelial cells in various diseases...
- Zigrino P, Ayachi O, Schild A, Kaltenberg J, Zamek J, Nischt R, et al. Loss of epidermal MMP-14 expression interferes with angiogenesis but not with re-epithelialization. Eur J Cell Biol. 2012;91:748-56 pubmed publisher..Taken together, these data indicate that MMP-14 expression in keratinocytes is dispensable for skin homeostasis and repair, but plays a crucial role in the epidermal-dermal crosstalk leading to modulation of vessel density...
- Legallicier B, Trugnan G, Murphy G, Lelongt B, Ronco P. Expression of the type IV collagenase system during mouse kidney development and tubule segmentation. J Am Soc Nephrol. 2001;12:2358-69 pubmed..These results suggest that a regulated balance of gelatinase activity is required during kidney organogenesis and that gelatinases continue to play a role in adult renal tubule physiology. ..
- Kierdorf K, Erny D, Goldmann T, Sander V, Schulz C, Perdiguero E, et al. Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat Neurosci. 2013;16:273-80 pubmed publisher..Our data provide cellular and molecular insights into the origin and development of microglia. ..
- Zigrino P, Brinckmann J, Niehoff A, Lu Y, Giebeler N, Eckes B, et al. Fibroblast-Derived MMP-14 Regulates Collagen Homeostasis in Adult Skin. J Invest Dermatol. 2016;136:1575-1583 pubmed publisher..Taken together, these data indicate that MMP-14 expression in fibroblasts plays a crucial role in collagen remodeling in adult skin and largely contributes to dermal homeostasis underlying its pathogenic role in fibrotic skin disease. ..
- Pons M, Cousins S, Alcazar O, Striker G, Marin Castano M. Angiotensin II-induced MMP-2 activity and MMP-14 and basigin protein expression are mediated via the angiotensin II receptor type 1-mitogen-activated protein kinase 1 pathway in retinal pigment epithelium: implications for age-related macular degener. Am J Pathol. 2011;178:2665-81 pubmed publisher..A better understanding of the molecular events by which Ang II induces ECM dysregulation is of critical importance to further define its contribution to the progression of sub-RPE deposits in AMD patients with HTN. ..
- Vasko R, Xavier S, Chen J, Lin C, Ratliff B, Rabadi M, et al. Endothelial sirtuin 1 deficiency perpetrates nephrosclerosis through downregulation of matrix metalloproteinase-14: relevance to fibrosis of vascular senescence. J Am Soc Nephrol. 2014;25:276-91 pubmed publisher..Our findings establish a novel mechanistic molecular link between endothelial SIRT1 depletion, downregulation of MMP-14, and the development of nephrosclerosis. ..
- Kachgal S, Carrion B, Janson I, Putnam A. Bone marrow stromal cells stimulate an angiogenic program that requires endothelial MT1-MMP. J Cell Physiol. 2012;227:3546-55 pubmed publisher..Other studies have debated the necessity of MT1-MMP in the context of vessel invasion in fibrin, but this study clearly demonstrates its requirement in BMSC-mediated angiogenesis. ..
- Ray A, Treloar H. IgSF8: a developmentally and functionally regulated cell adhesion molecule in olfactory sensory neuron axons and synapses. Mol Cell Neurosci. 2012;50:238-49 pubmed publisher..These data support the hypothesis that IgSF8 facilitates OSN synapse formation. ..
- Oh J, Takahashi R, Kondo S, Mizoguchi A, Adachi E, Sasahara R, et al. The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell. 2001;107:789-800 pubmed..These results support a role for RECK in the regulation of MMP-2 in vivo and implicate RECK downregulation in tumor angiogenesis. ..
- Chun T, Inoue M, Morisaki H, Yamanaka I, Miyamoto Y, Okamura T, et al. Genetic link between obesity and MMP14-dependent adipogenic collagen turnover. Diabetes. 2010;59:2484-94 pubmed publisher..and degradation of type I collagen at early stages of high-fat diet feeding was assessed in wild-type or MMP14 (MT1-MMP)-haploinsufficient mice using immunofluorescent staining and scanning electron microscopy...
- Chan K, Wong H, Jin G, Liu B, Cao R, Cao Y, et al. MT1-MMP inactivates ADAM9 to regulate FGFR2 signaling and calvarial osteogenesis. Dev Cell. 2012;22:1176-90 pubmed publisherb>MMP14 encodes a membrane-tethered metalloproteinase MT1-MMP, capable of remodeling the extracellular matrix and modulating receptors on the cell surface. Loss of MT1-MMP results in craniofacial abnormalities...
- Genís L, Gonzalo P, Tutor A, Galvez B, Martínez Ruiz A, Zaragoza C, et al. Functional interplay between endothelial nitric oxide synthase and membrane type 1 matrix metalloproteinase in migrating endothelial cells. Blood. 2007;110:2916-23 pubmed..MT1-MMP thus appears to be a key molecular effector of NO during the EC migration and angiogenic processes, and is a potential therapeutic target for NO-associated vascular disorders. ..
- Guyot R, Magre S, Leduque P, le Magueresse Battistoni B. Differential expression of tissue inhibitor of metalloproteinases type 1 (TIMP-1) during mouse gonad development. Dev Dyn. 2003;227:357-66 pubmed..Experiments are now under way to determine to what extent TIMP-1 is a morphogenic gene involved in seminiferous cord formation and development. ..
- Rozanov D, Savinov A, Golubkov V, Tomlinson S, Strongin A. Interference with the complement system by tumor cell membrane type-1 matrix metalloproteinase plays a significant role in promoting metastasis in mice. Cancer Res. 2006;66:6258-63 pubmed..We believe that our results shed additional light on the functions of MT1-MMP in cancer and clearly make this protease a promising drug target in metastatic malignancies. ..
- Hara T, Mimura K, Seiki M, Sakamoto T. Genetic dissection of proteolytic and non-proteolytic contributions of MT1-MMP to macrophage invasion. Biochem Biophys Res Commun. 2011;413:277-81 pubmed publisher..The proteolytic activity of MT1-MMP was not affected by the lack of APBA3 in macrophages. Apba3(-/-) and Mmp14(-/-) macrophages exhibited a 55% reduction of ATP levels compared to wild-type (WT) cells and the rate of motility ..
- Mirastschijski U, Zhou Z, Rollman O, Tryggvason K, AGren M. Wound healing in membrane-type-1 matrix metalloproteinase-deficient mice. J Invest Dermatol. 2004;123:600-2 pubmed
- Galvez B, Genís L, Matías Román S, Oblander S, Tryggvason K, Apte S, et al. Membrane type 1-matrix metalloproteinase is regulated by chemokines monocyte-chemoattractant protein-1/ccl2 and interleukin-8/CXCL8 in endothelial cells during angiogenesis. J Biol Chem. 2005;280:1292-8 pubmed
- Madsen D, Engelholm L, Ingvarsen S, Hillig T, Wagenaar Miller R, Kjøller L, et al. Extracellular collagenases and the endocytic receptor, urokinase plasminogen activator receptor-associated protein/Endo180, cooperate in fibroblast-mediated collagen degradation. J Biol Chem. 2007;282:27037-45 pubmed
- Riggins K, Mernaugh G, Su Y, Quaranta V, Koshikawa N, Seiki M, et al. MT1-MMP-mediated basement membrane remodeling modulates renal development. Exp Cell Res. 2010;316:2993-3005 pubmed publisher..Together these data suggest an important role for MT1-MMP in kidney development, which is mediated by its ability to regulate cell proliferation and migration by proteolytically cleaving kidney basement membrane components. ..
- Szabova L, Chrysovergis K, Yamada S, Holmbeck K. MT1-MMP is required for efficient tumor dissemination in experimental metastatic disease. Oncogene. 2008;27:3274-81 pubmed..The data demonstrate directly that MT1-MMP-mediated proteolysis by stromal cells is important in the metastatic process. ..
- Ranjan A, Kalraiya R. Invasive potential of melanoma cells correlates with the expression of MT1-MMP and regulated by modulating its association with motility receptors via N-glycosylation on the receptors. Biomed Res Int. 2014;2014:804680 pubmed publisher..The results thus demonstrate that the cancer cells use multiple mechanisms for degradation of matrix in a controlled manner to couple it with movement for effective invasion. ..
- Savinov A, Rozanov D, Golubkov V, Wong F, Strongin A. Inhibition of membrane type-1 matrix metalloproteinase by cancer drugs interferes with the homing of diabetogenic T cells into the pancreas. J Biol Chem. 2005;280:27755-8 pubmed..Overall, our studies have divulged a previously unknown function of MT1-MMP and identified a promising novel drug target in type I diabetes. ..
- Proulx Bonneau S, Guezguez A, Annabi B. A concerted HIF-1?/MT1-MMP signalling axis regulates the expression of the 3BP2 adaptor protein in hypoxic mesenchymal stromal cells. PLoS ONE. 2011;6:e21511 pubmed publisher..These mechanistic observations support the potential for malignant transformation of MSC within hypoxic tumour stroma and may contribute to evasion of the immune system by a tumour. ..
- Han K, Fahd D, Tshionyi M, Allemann N, Jain S, Chang J, et al. MT1-MMP modulates bFGF-induced VEGF-A expression in corneal fibroblasts. Protein Pept Lett. 2012;19:1334-9 pubmed..Here, we elaborate on the facilitative role of MMPs-specifically Membrane Type 1 MMP (MT1-MMP, MMP14)-in corneal NV...
- Johansson N, Ahonen M, Kahari V. Matrix metalloproteinases in tumor invasion. Cell Mol Life Sci. 2000;57:5-15 pubmed..In this review, we discuss the current concept concerning the role of MMPs and their inhibitors in tumor invasion, as a basis for prognosis and targeted therapeutic intervention in cancer. ..
- Swayampakula M, McDonald P, Vallejo M, Coyaud E, Chafe S, Westerback A, et al. The interactome of metabolic enzyme carbonic anhydrase IX reveals novel roles in tumor cell migration and invadopodia/MMP14-mediated invasion. Oncogene. 2017;36:6244-6261 pubmed publisher..include metabolic transporters, Î²1 integrins, integrin-associated protein CD98hc and matrix metalloprotease 14 (MMP14)...
- Moss N, Barbolina M, Liu Y, Sun L, Munshi H, Stack M. Ovarian cancer cell detachment and multicellular aggregate formation are regulated by membrane type 1 matrix metalloproteinase: a potential role in I.p. metastatic dissemination. Cancer Res. 2009;69:7121-9 pubmed publisher..of the collagen-rich submesothelial matrix to anchor secondary lesions, and acquisition of membrane type 1 matrix metalloproteinase (MT1-MMP; MMP-14) expression promotes a collagen-invasive phenotype in ovarian carcinoma...
- Mimura T, Han K, Onguchi T, Chang J, Kim T, Kojima T, et al. MT1-MMP-mediated cleavage of decorin in corneal angiogenesis. J Vasc Res. 2009;46:541-50 pubmed publisher..The proangiogenic role of MT1-MMP in the cornea may be mediated, in part, by facilitated cleavage of corneal decorin. ..
- Tang Y, Rowe R, Botvinick E, Kurup A, Putnam A, Seiki M, et al. MT1-MMP-dependent control of skeletal stem cell commitment via a ?1-integrin/YAP/TAZ signaling axis. Dev Cell. 2013;25:402-16 pubmed publisher..Here we demonstrate that conditional deletion of the membrane-anchored metalloproteinase MT1-MMP (Mmp14) in mesenchymal progenitors, but not in committed osteoblasts, redirects SSC fate decisions from osteogenesis to ..
- Koziol A, Gonzalo P, Mota A, Pollán A, Lorenzo C, Colome N, et al. The protease MT1-MMP drives a combinatorial proteolytic program in activated endothelial cells. FASEB J. 2012;26:4481-94 pubmed publisher..This novel concept of MT1-MMP-driven combinatorial proteolysis in angiogenesis might be extendable to proteolytic actions in other cellular contexts. ..
- Schneider F, Sukhova G, Aikawa M, Canner J, Gerdes N, Tang S, et al. Matrix-metalloproteinase-14 deficiency in bone-marrow-derived cells promotes collagen accumulation in mouse atherosclerotic plaques. Circulation. 2008;117:931-9 pubmed publisher..Because Mmp14-/- mice die by 3 weeks of age, this study used lethally irradiated low-density lipoprotein receptor-deficient mice ..
- Tanaka M, Sato H, Takino T, Iwata K, Inoue M, Seiki M. Isolation of a mouse MT2-MMP gene from a lung cDNA library and identification of its product. FEBS Lett. 1997;402:219-22 pubmed..A monoclonal antibody raised against a synthetic peptide recognized mouse MT2-MMP as a 70 kDa protein. Like MT1- and MT3-MMPs, mouse MT2-MMP caused activation of progelatinase A upon co-transfection into COS-1 cells. ..
- Otani S, Kakinuma S, Kamiya A, Goto F, Kaneko S, Miyoshi M, et al. Matrix metalloproteinase-14 mediates formation of bile ducts and hepatic maturation of fetal hepatic progenitor cells. Biochem Biophys Res Commun. 2016;469:1062-8 pubmed publisher..We demonstrate that MMP-14-mediated signaling in fetal hepatic progenitor cells promotes biliary luminal formation around the portal vein and negatively controls the maturation of hepatocytes. ..
- Chellaiah M, Ma T. Membrane localization of membrane type 1 matrix metalloproteinase by CD44 regulates the activation of pro-matrix metalloproteinase 9 in osteoclasts. Biomed Res Int. 2013;2013:302392 pubmed publisher..Surface expression of CD44, membrane localization of MT1-MMP, and activation of pro-MMP9 are the necessary sequence of events in osteoclast migration...
- Gkantidis N, Blumer S, Katsaros C, Graf D, Chiquet M. Site-specific expression of gelatinolytic activity during morphogenesis of the secondary palate in the mouse embryo. PLoS ONE. 2012;7:e47762 pubmed publisher..Mmp2 and Mmp14 (MT1-MMP), but not Mmp9 and Mmp13, mRNAs were expressed in the mesenchyme around the epithelial folds of the ..
- Nakano Y, Forsprecher J, Kaartinen M. Regulation of ATPase activity of transglutaminase 2 by MT1-MMP: implications for mineralization of MC3T3-E1 osteoblast cultures. J Cell Physiol. 2010;223:260-9 pubmed publisher..Based on these data, we propose that MT1-MMP modulates the extracellular function TG2 as part of a regulatory mechanism activates the pro-mineralization function of TG2. ..
- Azar D, Casanova F, Mimura T, Jain S, Chang J. Effect of MT1-MMP deficiency and overexpression in corneal keratocytes on vascular endothelial cell migration and proliferation. Curr Eye Res. 2008;33:954-62 pubmed publisher..4+/-3.6%) than WT/MT1-MMP-transfected keratocytes (119.7+/-2.2%; p<0.001). Migration assays confirmed these findings. Keratocyte-derived MT1-MMP has anti-angiogenic effects in CPAE cells. ..
- Croissandeau G, Chretien M, Mbikay M. Involvement of matrix metalloproteinases in the adipose conversion of 3T3-L1 preadipocytes. Biochem J. 2002;364:739-46 pubmed..It did, however, markedly reduce C/EBPbeta DNA-binding capacity. Taken together, these results suggest that MMPs, and notably MMP-2 and MMP-9, may be necessary mediators of adipocytic differentiation of 3T3-L1 cells. ..
- Beertsen W, Holmbeck K, Niehof A, Bianco P, Chrysovergis K, Birkedal Hansen H, et al. On the role of MT1-MMP, a matrix metalloproteinase essential to collagen remodeling, in murine molar eruption and root growth. Eur J Oral Sci. 2002;110:445-51 pubmed..These observations indicate that MT1-MMP plays a central role in periodontal remodeling. The stunted root growth and the failure to erupt indicate the important role of the enzyme in tooth development. ..
- Zavadzkas J, Mukherjee R, Rivers W, Patel R, Meyer E, Black L, et al. Direct regulation of membrane type 1 matrix metalloproteinase following myocardial infarction causes changes in survival, cardiac function, and remodeling. Am J Physiol Heart Circ Physiol. 2011;301:H1656-66 pubmed publisherThe membrane type 1 matrix metalloproteinase (MT1-MMP) is increased in left ventricular (LV) failure...
- Hikita A, Kadono Y, Chikuda H, Fukuda A, Wakeyama H, Yasuda H, et al. Identification of an alternatively spliced variant of Ca2+-promoted Ras inactivator as a possible regulator of RANKL shedding. J Biol Chem. 2005;280:41700-6 pubmed..deltaCAPRI or a constitutive active form of Ras up-regulated the expression level of matrix-metalloproteinase 14 (MMP14), which directly cleaves the ectodomain of RANKL, whereas Erk activation by expressing the constitutive active ..
- Ryu J, Vicencio A, Yeager M, Kashgarian M, Haddad G, Eickelberg O. Differential expression of matrix metalloproteinases and their inhibitors in human and mouse lung development. Thromb Haemost. 2005;94:175-83 pubmed..MMP-2, TIMP-2, and TIMP-3 may be key regulatory enzymes during lung development, possibly through their complex action on ECM components, membrane receptor ectodomain shedding, and growth factor bioactivity. ..
- Sakakura Y, Hosokawa Y, Tsuruga E, Irie K, Nakamura M, Yajima T. Contributions of matrix metalloproteinases toward Meckel's cartilage resorption in mice: immunohistochemical studies, including comparisons with developing endochondral bones. Cell Tissue Res. 2007;328:137-51 pubmed..These results indicate that the degradation of Meckel's cartilage involves an activation cascade of MMPs that differs from that in endochondral bone formation. ..
- Wang Z, Zhang F, He J, Wu P, Tay L, Cai M, et al. Binding of PLD2-Generated Phosphatidic Acid to KIF5B Promotes MT1-MMP Surface Trafficking and Lung Metastasis of Mouse Breast Cancer Cells. Dev Cell. 2017;43:186-197.e7 pubmed publisher..Taken together, these results identify a role of PLD2-generated PA in the regulation of kinesin-1 motor functions and breast cancer metastasis and suggest PLD2 as a potential therapeutic target for metastatic breast cancer. ..
- Talmi Frank D, Altboum Z, Solomonov I, Udi Y, Jaitin D, Klepfish M, et al. Extracellular Matrix Proteolysis by MT1-MMP Contributes to Influenza-Related Tissue Damage and Mortality. Cell Host Microbe. 2016;20:458-470 pubmed publisher..This study highlights the importance of tissue resilience in surviving infection and the potential of such host-pathogen therapy combinations for respiratory infections. ..
- Beertsen W, Holmbeck K, Niehof A, Bianco P, Chrysovergis K, Birkedal Hansen H, et al. Inhibition of molar eruption and root elongation in MT1-MMP-deficient mice. Connect Tissue Res. 2003;44 Suppl 1:298-9 pubmed..It was shown that in deficient animals, eruption and root elongation were severely inhibited, signifying a role of the enzyme in these developmental processes. ..
- Wang K, Yamamoto H, Chin J, Werb Z, Vu T. Epidermal growth factor receptor-deficient mice have delayed primary endochondral ossification because of defective osteoclast recruitment. J Biol Chem. 2004;279:53848-56 pubmed..EGFR signaling regulated osteoclast formation. Inhibition of EGFR tyrosine kinase activity decreased the generation of osteoclasts from cultured bone marrow cells. ..
- Brezillon S, Pietraszek K, Maquart F, Wegrowski Y. Lumican effects in the control of tumour progression and their links with metalloproteinases and integrins. FEBS J. 2013;280:2369-81 pubmed publisher..This review summarizes recent data concerning lumican control of tumour progression in different cancers, with a particular focus on its interactions with MMPs and integrins. Its potential therapeutic implications are discussed. ..
- Ingvarsen S, Madsen D, Hillig T, Lund L, Holmbeck K, Behrendt N, et al. Dimerization of endogenous MT1-MMP is a regulatory step in the activation of the 72-kDa gelatinase MMP-2 on fibroblasts and fibrosarcoma cells. Biol Chem. 2008;389:943-53 pubmed publisher..Since only a negligible level of proMMP-2 activation was obtained with MT1-MMP-expressing cells in the absence of dimerization, our results identify the dimerization event as a critical level of proteolytic cascade regulation. ..
- Mori H, Lo A, Inman J, Alcaraz J, Ghajar C, Mott J, et al. Transmembrane/cytoplasmic, rather than catalytic, domains of Mmp14 signal to MAPK activation and mammary branching morphogenesis via binding to integrin ?1. Development. 2013;140:343-52 pubmed publisher..Because the cell membrane-bound matrix metalloproteinase Mmp14 is known to play a key role in cancer cell invasion, we hypothesized that it could also be centrally involved in ..
- Kandalam V, Basu R, Abraham T, Wang X, Soloway P, Jaworski D, et al. TIMP2 deficiency accelerates adverse post-myocardial infarction remodeling because of enhanced MT1-MMP activity despite lack of MMP2 activation. Circ Res. 2010;106:796-808 pubmed publisher..TIMP2 replenishment in diseased myocardium could provide a potential therapy in reducing or preventing disease progression. ..
- Perez S, Cano D, Dao Pick T, Rougier J, Werb Z, Hebrok M. Matrix metalloproteinases 2 and 9 are dispensable for pancreatic islet formation and function in vivo. Diabetes. 2005;54:694-701 pubmed..However, islet formation is unaffected in transgenic mice with modified tissue inhibitor of metalloproteinase-1 (TIMP1) levels, suggesting that MMP activity may contribute little to islet morphogenesis in vivo. ..
- Xiong W, Knispel R, Mactaggart J, Greiner T, Weiss S, Baxter B. Membrane-type 1 matrix metalloproteinase regulates macrophage-dependent elastolytic activity and aneurysm formation in vivo. J Biol Chem. 2009;284:1765-71 pubmed publisher..These studies demonstrate that destruction of the elastin fiber network during AAA formation is dependent on macrophage-derived MT1-MMP, which unexpectedly serves as a direct-acting regulator of macrophage proteolytic activity. ..
- Spinale F, Mukherjee R, Zavadzkas J, Koval C, Bouges S, Stroud R, et al. Cardiac restricted overexpression of membrane type-1 matrix metalloproteinase causes adverse myocardial remodeling following myocardial infarction. J Biol Chem. 2010;285:30316-27 pubmed publisher..Thus, a proteolytically diverse portfolio exists for MT1-MMP within the myocardium and likely plays a mechanistic role in adverse LV remodeling. ..