Gene Symbol: MMP17
Description: matrix metallopeptidase 17
Alias: MMP-17, MT4-MMP, MT4MMP, MTMMP4, matrix metalloproteinase-17, MT-MMP 4, matrix metallopeptidase 17 (membrane-inserted), matrix metalloproteinase 17 (membrane-inserted), membrane-type matrix metalloproteinase 4, membrane-type-4 matrix metalloproteinase
Species: human
Products:     MMP17

Top Publications

  1. Terp G, Christensen I, Jørgensen F. Structural differences of matrix metalloproteinases. Homology modeling and energy minimization of enzyme-substrate complexes. J Biomol Struct Dyn. 2000;17:933-46 pubmed
    ..Differences in the P1' pocket are well-documented and have been extensively exploited in inhibitor design. The present work indicates that selectivity could be further improved by considering the P2 pocket as well. ..
  2. Jung M, Römer A, Keyszer G, Lein M, Kristiansen G, Schnorr D, et al. mRNA expression of the five membrane-type matrix metalloproteinases MT1-MT5 in human prostatic cell lines and their down-regulation in human malignant prostatic tissue. Prostate. 2003;55:89-98 pubmed
    ..It seems to occur mainly in epithelial cells and has to be examined as special characteristic of this tumor entity in further studies. ..
  3. Yip C, Foidart P, Noel A, Sounni N. MT4-MMP: The GPI-Anchored Membrane-Type Matrix Metalloprotease with Multiple Functions in Diseases. Int J Mol Sci. 2019;20: pubmed publisher
    MT4-MMP (or MMP17) belongs to the Membrane-Type Matrix Metalloproteinase (MT-MMP) family...
  4. Foidart P, Yip C, Radermacher J, Blacher S, Lienard M, Montero Ruiz L, et al. Expression of MT4-MMP, EGFR, and RB in Triple-Negative Breast Cancer Strongly Sensitizes Tumors to Erlotinib and Palbociclib Combination Therapy. Clin Cancer Res. 2018;: pubmed publisher
  5. Xiao Y, Li B, Liu J. miRNA?27a regulates arthritis via PPAR? in vivo and in vitro. Mol Med Rep. 2018;17:5454-5462 pubmed publisher
    ..The PPAR? inhibitor reduced the function of miR?27a downregulation on arthritis. Therefore the results of the present study revealed that miR?27a regulates arthritis via PPAR?. ..
  6. Salz T, Deng C, Pampo C, Siemann D, Qiu Y, Brown K, et al. Histone Methyltransferase hSETD1A Is a Novel Regulator of Metastasis in Breast Cancer. Mol Cancer Res. 2015;13:461-9 pubmed publisher
    ..Furthermore, a group of matrix metalloproteinases (including MMP2, MMP9, MMP12, MMP13, and MMP17) were identified which were downregulated upon depletion of hSETD1A and demonstrated a decrease in H3K4me3 at ..
  7. Ariyoshi W, Takahashi N, Hida D, Knudson C, Knudson W. Mechanisms involved in enhancement of the expression and function of aggrecanases by hyaluronan oligosaccharides. Arthritis Rheum. 2012;64:187-97 pubmed publisher
    ..Disruptive changes in chondrocyte-matrix interactions by HA oligosaccharides induce matrix degradation and elevate aggrecanases via the activation of the NF-?B signaling pathway. ..
  8. Martín Alonso M, García Redondo A, Guo D, Camafeita E, Martínez F, Alfranca A, et al. Deficiency of MMP17/MT4-MMP proteolytic activity predisposes to aortic aneurysm in mice. Circ Res. 2015;117:e13-26 pubmed publisher
    ..To determine the role of the protease MMP17/MT4-MMP in the arterial wall and its possible relevance in human aortic pathology...
  9. Itoh Y, Kajita M, Kinoh H, Mori H, Okada A, Seiki M. Membrane type 4 matrix metalloproteinase (MT4-MMP, MMP-17) is a glycosylphosphatidylinositol-anchored proteinase. J Biol Chem. 1999;274:34260-6 pubmed
    ..GPI anchoring of MT4-MMP on the cell surface indicates a unique biological function and character for this proteinase. ..

More Information


  1. Nimri L, Barak H, Graeve L, Schwartz B. Restoration of caveolin-1 expression suppresses growth, membrane-type-4 metalloproteinase expression and metastasis-associated activities in colon cancer cells. Mol Carcinog. 2013;52:859-70 pubmed publisher
    ..We conclude that cav-1 orchestrates and reorganize several proteins in lipid rafts, activities directly associated with reduced tumorigenic and metastatic ability of colon cancer cells. ..
  2. Gauthier M, Racine C, Ferland C, Flamand N, Chakir J, Tremblay G, et al. Expression of membrane type-4 matrix metalloproteinase (metalloproteinase-17) by human eosinophils. Int J Biochem Cell Biol. 2003;35:1667-73 pubmed
    ..Consequently, MT4-MMP may be directly involved in the degradation of extracellular matrix components and/or modulate the activity of other proteins implicated in eosinophil migration and tissue remodeling. ..
  3. Blanco M, Rodriguez Martin I, Learte A, Clemente C, Montalvo M, Seiki M, et al. Developmental expression of membrane type 4-matrix metalloproteinase (Mt4-mmp/Mmp17) in the mouse embryo. PLoS ONE. 2017;12:e0184767 pubmed publisher
    ..Within this family, we focused our study on Mt4-mmp (also called Mmp17) that belongs to a distinct subset that is anchored to the cell surface via a glycosylphosphatidylinositol (GPI) ..
  4. Atkinson S, Roghi C, Murphy G. MT1-MMP hemopexin domain exchange with MT4-MMP blocks enzyme maturation and trafficking to the plasma membrane in MCF7 cells. Biochem J. 2006;398:15-22 pubmed
  5. Gao G, Plaas A, Thompson V, Jin S, Zuo F, Sandy J. ADAMTS4 (aggrecanase-1) activation on the cell surface involves C-terminal cleavage by glycosylphosphatidyl inositol-anchored membrane type 4-matrix metalloproteinase and binding of the activated proteinase to chondroitin sulfate and heparan sulfate . J Biol Chem. 2004;279:10042-51 pubmed
    ..We conclude that ADAMTS-4 activation in this cell system involves the coordinated activity of both glycosylphosphatidyl inositol-anchored MT4-MMP and the proteoglycan form of syndecan-1 on the cell surface. ..
  6. Host L, Paye A, Detry B, Blacher S, Munaut C, Foidart J, et al. The proteolytic activity of MT4-MMP is required for its pro-angiogenic and pro-metastatic promoting effects. Int J Cancer. 2012;131:1537-48 pubmed publisher
    ..It identifies MT4-MMP as a key intrinsic tumor cell determinant that contributes to the elaboration of a permissive microenvironment for metastatic dissemination. ..
  7. Huang C, Yang W, Chang S, Tai S, Tzeng C, Kao J, et al. Regulation of membrane-type 4 matrix metalloproteinase by SLUG contributes to hypoxia-mediated metastasis. Neoplasia. 2009;11:1371-82 pubmed
    ..These findings establish a novel signaling pathway for hypoxia-mediated metastasis and elucidate the underlying regulatory mechanism and functional significance of MT4-MMP in cancer metastasis. ..
  8. Liang B, Xiao T, Long J, Liu M, Li Z, Liu S, et al. Hydrogen sulfide alleviates myocardial fibrosis in mice with alcoholic cardiomyopathy by downregulating autophagy. Int J Mol Med. 2017;40:1781-1791 pubmed publisher
    ..autophagy-associated proteins (Beclin 1, Atg3 and Atg7) and fibrosis-associated proteins (MMP8, MMP13, MMP14, MMP17 and TGF-?1), as well as miR-21 and miR-221. These results were markedly reversed following treatment with H2S...
  9. English W, Puente X, Freije J, Knauper V, Amour A, Merryweather A, et al. Membrane type 4 matrix metalloproteinase (MMP17) has tumor necrosis factor-alpha convertase activity but does not activate pro-MMP2. J Biol Chem. 2000;275:14046-55 pubmed
    b>Membrane type 4 matrix metalloproteinase (MT4-MMP) shows the least sequence homology to the other MT-MMPs, suggesting a distinct function for this protein...
  10. Wang Y, Johnson A, Ye Q, Dyer R. Catalytic activities and substrate specificity of the human membrane type 4 matrix metalloproteinase catalytic domain. J Biol Chem. 1999;274:33043-9 pubmed
    ..MT4-MMP is, therefore, a competent Zn(2+)-dependent MMP with unique specificity among synthetic substrates and the capability to both degrade gelatin and activate progelatinase A. ..
  11. Puente X, Pendas A, Llano E, Velasco G, Lopez Otin C. Molecular cloning of a novel membrane-type matrix metalloproteinase from a human breast carcinoma. Cancer Res. 1996;56:944-9 pubmed
    ..On the basis of these expression data in breast tumors, a potential role for human MT4-MMP in the tumoral process is also suggested. ..
  12. Puente X, Pendas A, Llano E, Lopez Otin C. Localization of the human membrane type 4-matrix metalloproteinase gene (MMP17) to chromosome 12q24. Genomics. 1998;54:578-9 pubmed
  13. Clemente C, Rius C, Alonso Herranz L, Martín Alonso M, Pollán Ã, Camafeita E, et al. MT4-MMP deficiency increases patrolling monocyte recruitment to early lesions and accelerates atherosclerosis. Nat Commun. 2018;9:910 pubmed publisher
    ..Our results suggest that MT4-MMP targeting may constitute a novel strategy to boost patrolling monocyte activity in early inflammation. ..
  14. Hieronimus B, Pfohl J, Busch C, Graeve L. Expression and Characterization of Membrane-Type 4 Matrix Metalloproteinase (MT4-MMP) and its Different Forms in Melanoma. Cell Physiol Biochem. 2017;42:198-210 pubmed publisher
    ..We demonstrate the novel expression of MT4-MMP in melanocytic tissues and propose a precursor/product-relationship of the different forms of MT4-MMP in melanoma cells. ..
  15. Yip C, Foidart P, Somja J, Truong A, Lienard M, Feyereisen E, et al. MT4-MMP and EGFR expression levels are key biomarkers for breast cancer patient response to chemotherapy and erlotinib. Br J Cancer. 2017;116:742-751 pubmed publisher
    ..We demonstrate that MT4-MMP defines a sub-population of TNBC sensitive to a combination of DNA-targeting chemotherapeutic agents and anti-EGFR drugs. ..
  16. Truong A, Yip C, Paye A, Blacher S, Munaut C, Deroanne C, et al. Dynamics of internalization and recycling of the prometastatic membrane type 4 matrix metalloproteinase (MT4-MMP) in breast cancer cells. FEBS J. 2016;283:704-22 pubmed publisher
    b>Membrane type 4 matrix metalloproteinase (MT4-MMP) [matrix metalloproteinase (MMP) 17] is a GPI-anchored membrane-type MMP expressed on the cell surface of human breast cancer cells...
  17. Kolkenbrock H, Essers L, Ulbrich N, Will H. Biochemical characterization of the catalytic domain of membrane-type 4 matrix metalloproteinase. Biol Chem. 1999;380:1103-8 pubmed
    A C-terminal truncated form of membrane-type 4 matrix metalloproteinase (MT4-MMP; MMP 17), lacking the hemopexin-like and transmembrane domain, was expressed in Escherichia coli...
  18. Paye A, Truong A, Yip C, Cimino J, Blacher S, Munaut C, et al. EGFR activation and signaling in cancer cells are enhanced by the membrane-bound metalloprotease MT4-MMP. Cancer Res. 2014;74:6758-70 pubmed publisher
    ..Altogether, our results identify MT4-MMP as a positive modifier of EGFR outside-in signaling that acts to cooperatively drive cancer cell proliferation. ..
  19. Freilinger T, Anttila V, de Vries B, Malik R, Kallela M, Terwindt G, et al. Genome-wide association analysis identifies susceptibility loci for migraine without aura. Nat Genet. 2012;44:777-82 pubmed publisher
    ..This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder. ..
  20. Sohail A, Marco M, Zhao H, Shi Q, Merriman S, Mobashery S, et al. Characterization of the dimerization interface of membrane type 4 (MT4)-matrix metalloproteinase. J Biol Chem. 2011;286:33178-89 pubmed publisher
    MT4-MMP (MMP17) belongs to a unique subset of membrane type-matrix metalloproteinases that are anchored to the cell surface via a glycosylphosphatidylinositol moiety. However, little is known about its biochemical properties...
  21. Chabottaux V, Ricaud S, Host L, Blacher S, Paye A, Thiry M, et al. Membrane-type 4 matrix metalloproteinase (MT4-MMP) induces lung metastasis by alteration of primary breast tumour vascular architecture. J Cell Mol Med. 2009;13:4002-13 pubmed publisher
    ..On this basis, we propose that MT4-MMP promotes lung metastasis by disturbing the tumour vessel integrity and thereby facilitating tumour cell intravasation. ..
  22. Rozanov D, Hahn Dantona E, Strickland D, Strongin A. The low density lipoprotein receptor-related protein LRP is regulated by membrane type-1 matrix metalloproteinase (MT1-MMP) proteolysis in malignant cells. J Biol Chem. 2004;279:4260-8 pubmed
    ..These events implicate MT1-MMP, not only in the activation of MMP-2, but also in the mechanisms that control the subsequent fate of MMP-2 in cells and tissues. ..
  23. Kinoh H, Hayashita H, Kajita M, Okada A, Seiki M. Assignment of the genes for membrane-type-4 matrix metalloproteinase (Mmp17, MMP17) to mouse chromosome 5, human chromosome band 12q24.3 and membrane-type-5 matrix metalloproteinase (Mmp24, MMP24) to mouse chromosome 2 and human chromosome band 20q11. Cytogenet Cell Genet. 1999;87:97-8 pubmed
  24. Kajita M, Kinoh H, Ito N, Takamura A, Itoh Y, Okada A, et al. Human membrane type-4 matrix metalloproteinase (MT4-MMP) is encoded by a novel major transcript: isolation of complementary DNA clones for human and mouse mt4-mmp transcripts. FEBS Lett. 1999;457:353-6 pubmed
    ..and failed to express protein, and the other is the major transcript that has an extended open reading frame and expressed 67 and 71 kDa translation products. Thus, functional mt4-mmp has been identified for the first time. ..