matrix metalloproteinase 14


Summary: A transmembrane domain-containing matrix metalloproteinase. It is synthesized as an inactive zymogen that is activated by the action of PROPROTEIN CONVERTASES such as FURIN. Matrix metalloproteinase 14 plays a direct role in the cleavage of proteins in the pericellular environment. In addition, it can function indirectly by enzymatically activating the proprotein form of MATRIX METALLOPROTEINASE 15.

Top Publications

  1. Lazarus S, Tseng H, Lawrence F, Woodruff M, Duncan E, Pettit A. Characterization of Normal Murine Carpal Bone Development Prompts Re-Evaluation of Pathologic Osteolysis as the Cause of Human Carpal-Tarsal Osteolysis Disorders. Am J Pathol. 2017;187:1923-1934 pubmed publisher
    ..Thus, abnormal peri-articular skeletal development and modeling, rather than excessive bone resorption, may be the underlying pathophysiology of these skeletal syndromes. ..
  2. Jessen T, Jessen J. VANGL2 interacts with integrin ?v to regulate matrix metalloproteinase activity and cell adhesion to the extracellular matrix. Exp Cell Res. 2017;361:265-276 pubmed publisher
    ..Lastly, we have identified integrin ?v?3 as a novel VANGL2 binding partner. Together, these findings begin to dissect the molecular underpinnings of how VANGL2 regulates MMP activity and cell adhesion to the ECM. ..
  3. Bruney L, Conley K, Moss N, Liu Y, Stack M. Membrane-type I matrix metalloproteinase-dependent ectodomain shedding of mucin16/ CA-125 on ovarian cancer cells modulates adhesion and invasion of peritoneal mesothelium. Biol Chem. 2014;395:1221-31 pubmed publisher
  4. 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. ..
  5. Lee Y, Park J, Cheon D, Kim T, Park Y, Oh E, et al. Processing of syndecan-2 by matrix metalloproteinase-14 and effect of its cleavage on VEGF-induced tube formation of HUVECs. Biochem J. 2017;474:3719-3732 pubmed publisher
    ..These results suggest that MMP-14 is a novel enzyme responsible for degrading SDC2 and impairing its physiological roles including angiogenesis...
  6. Yahata T, Ibrahim A, Muguruma Y, Eren M, Shaffer A, Watanabe N, et al. TGF-?-induced intracellular PAI-1 is responsible for retaining hematopoietic stem cells in the niche. Blood. 2017;130:2283-2294 pubmed publisher
    ..Our findings open up a new field for the study of intracellular proteolysis as a regulatory mechanism of stem cell fate, which has the potential to improve clinical HSPC mobilization and transplantation protocols. ..
  7. Yang J, Kasberg W, Celo A, Liang Z, Quispe K, Stack M. Post-translational modification of the membrane type 1 matrix metalloproteinase (MT1-MMP) cytoplasmic tail impacts ovarian cancer multicellular aggregate dynamics. J Biol Chem. 2017;292:13111-13121 pubmed publisher
    ..Together, these findings suggest that post-translational regulation of the Thr567 in the MT1-MMP cytoplasmic tail may function as a regulatory mechanism to impact ovarian cancer metastatic success. ..
  8. Liu B, Pang B, Wang Q, Yang S, Gao T, Ding Q, et al. EZH2 upregulation correlates with tumor invasiveness, proliferation, and angiogenesis in human pituitary adenomas. Hum Pathol. 2017;66:101-107 pubmed publisher
    ..This is the first report to describe EZH2 overexpression in human PAs, especially invasive adenomas. Thus, EZH2 is a potentially useful diagnostic marker and pharmacotherapeutic target for invasive PAs. ..
  9. Fujii M, Yoneda A, Takei N, Sakai Sawada K, Kosaka M, Minomi K, et al. Endoplasmic reticulum oxidase 1? is critical for collagen secretion from and membrane type 1-matrix metalloproteinase levels in hepatic stellate cells. J Biol Chem. 2017;292:15649-15660 pubmed publisher
    ..The results suggest that ERO1? plays a crucial role in HSC proliferation via posttranslational modification of collagen and MT1-MMP and, therefore, may be a suitable therapeutic target for managing liver fibrosis. ..

More Information


  1. Brasher M, Martynowicz D, Grafinger O, Hucik A, Shanks Skinner E, Uniacke J, et al. Interaction of Munc18c and syntaxin4 facilitates invadopodium formation and extracellular matrix invasion of tumor cells. J Biol Chem. 2017;292:16199-16210 pubmed publisher
    ..Our findings implicate Munc18c as a regulator of Stx4-mediated trafficking of MT1-MMP and EGFR, advancing our understanding of the role of SNARE function in the localization of proteins that drive tumor cell invasion. ..
  2. Hohensinner P, Baumgartner J, Kral Pointner J, Uhrin P, Ebenbauer B, Thaler B, et al. PAI-1 (Plasminogen Activator Inhibitor-1) Expression Renders Alternatively Activated Human Macrophages Proteolytically Quiescent. Arterioscler Thromb Vasc Biol. 2017;37:1913-1922 pubmed publisher
    ..We were able to demonstrate matrix degradation dependent on membrane-bound proteases in proinflammatory stimulated macrophages and a forced proteolytical quiescence in alternatively polarized macrophages by the expression of PAI-1. ..
  3. Kopinke D, Roberson E, Reiter J. Ciliary Hedgehog Signaling Restricts Injury-Induced Adipogenesis. Cell. 2017;170:340-351.e12 pubmed publisher
    ..We conclude that ciliary Hh signaling by FAPs orchestrates the regenerative response to skeletal muscle injury. ..
  4. Haas T, Stitelman D, Davis S, Apte S, Madri J. Egr-1 mediates extracellular matrix-driven transcription of membrane type 1 matrix metalloproteinase in endothelium. J Biol Chem. 1999;274:22679-85 pubmed
  5. Fukai Y, Ohsawa Y, Ohtsubo H, Nishimatsu S, Hagiwara H, Noda M, et al. Cleavage of ?-dystroglycan occurs in sarcoglycan-deficient skeletal muscle without MMP-2 and MMP-9. Biochem Biophys Res Commun. 2017;492:199-205 pubmed publisher
    ..Thus, matrix metalloproteinases contributing to ?-dystroglycan cleavage are redundant, and MMP-14 could participate in the pathogenesis of sarcoglycanopathy. ..
  6. Klymenko Y, Kim O, Loughran E, Yang J, Lombard R, Alber M, et al. Cadherin composition and multicellular aggregate invasion in organotypic models of epithelial ovarian cancer intraperitoneal metastasis. Oncogene. 2017;36:5840-5851 pubmed publisher
    ..Collectively, our data emphasize the role of Ncad in intraperitoneal seeding of EOC and provide the rationale for future studies targeting Ncad in preclinical models of EOC metastasis. ..
  7. Sakamoto T, Seiki M. Integrated functions of membrane-type 1 matrix metalloproteinase in regulating cancer malignancy: Beyond a proteinase. Cancer Sci. 2017;108:1095-1100 pubmed publisher
    ..In this review, we summarize recent findings relating to how MT1-MMP activates HIF and its effects on cancer cells and stromal cells. ..
  8. Yamamoto K, Santamaria S, Botkjaer K, Dudhia J, Troeberg L, Itoh Y, et al. Inhibition of Shedding of Low-Density Lipoprotein Receptor-Related Protein 1 Reverses Cartilage Matrix Degradation in Osteoarthritis. Arthritis Rheumatol. 2017;69:1246-1256 pubmed publisher
    ..Shedding of LRP-1 is a key link to OA progression. Local inhibition of LRP-1 sheddase activities of ADAM-17 and MMP-14 is a unique way to reverse matrix degradation in OA cartilage and could be effective as a therapeutic approach. ..
  9. Roth E, Cao J. miR-181 suppresses metastasis via MMP-14. Aging (Albany NY). 2015;7:740-1 pubmed
  10. Nguyen A, Chia J, Ros M, Hui K, Saltel F, Bard F. Organelle Specific O-Glycosylation Drives MMP14 Activation, Tumor Growth, and Metastasis. Cancer Cell. 2017;32:639-653.e6 pubmed publisher
    ..Together, our results indicate that GALNTs strongly promote liver tumor growth after relocating to the ER. ..
  11. Figueroa D, Kemeny S, Clyne A. Glycated collagen decreased endothelial cell fibronectin alignment in response to cyclic stretch via interruption of actin alignment. J Biomech Eng. 2014;136:101010 pubmed publisher
    ..These data demonstrate the importance of endothelial cell actin tension in remodeling and aligning matrix proteins in response to mechanical stimuli, which is critical to vascular remodeling in health and disease. ..