This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takino, T. Articles by Sato, H. Search for Related Content PubMed PubMed Citation Articles by Takino, T. Articles by Sato, H.

Membrane Type 1 Matrix Metalloproteinase Regulates Collagen-Dependent Mitogen-Activated Protein/Extracellular Signal-Related Kinase Activation and Cell Migration

Departments of ¹ Molecular Virology and Oncology and ² Cell Cycle Regulation, Cancer Research Institute, Kanazawa University, Kanazawa, and ³ Division of Cancer Cell Research, Institute of Medical Science, University of Tokyo, Tokyo, Japan

Mitogen-activated protein kinase-extracellular signal-related kinase (ERK) kinase 1 (MEK1)/ERK signaling has been implicated in the regulation of tumor cell invasion and metastasis. Migration of HT1080 cells on type I collagen was suppressed by the matrix metalloproteinase (MMP) inhibitors BB94 and tissue inhibitor of metalloproteinase (TIMP)-2 but not by TIMP-1. TIMP-2-specific inhibition suggests that membrane type 1 MMP (MT1-MMP) is likely involved in this process. Activation of ERK was induced in HT1080 cells adhered on dishes coated with type I collagen, and this was inhibited by BB94. MMP-2 processing in HT1080 cells, which also was stimulated by cultivation on type I collagen, was inhibited by MEK inhibitor PD98059. Expression of a constitutively active form of MEK1 promoted MMP-2 processing concomitant with the increase of MT1-MMP levels, suggesting that MT1-MMP is regulated by MEK/ERK signaling. In addition, expression of the hemopexin-like domain of MT1-MMP in HT1080 cells interfered with MMP-2 processing, ERK activation, and cell migration, implying that the enzymatic activity of MT1-MMP is involved in collagen-induced ERK activation, which results in enhanced cell migration. Thus, adhesion of HT1080 cells to type I collagen induces MT1-MMP-dependent ERK activation, which in turn causes an increase in MT1-MMP levels and subsequent cell migration.

This article has been cited by other articles:

				T. Onguchi, K. Y. Han, J.-H. Chang, and D. T. Azar Membrane Type-1 Matrix Metalloproteinase Potentiates Basic Fibroblast Growth Factor-Induced Corneal Neovascularization Am. J. Pathol., April 1, 2009; 174(4): 1564 - 1571. [Abstract] [Full Text] [PDF]

				Y. Nishida, H. Miyamori, E. W. Thompson, T. Takino, Y. Endo, and H. Sato Activation of Matrix Metalloproteinase-2 (MMP-2) by Membrane Type 1 Matrix Metalloproteinase through an Artificial Receptor for ProMMP-2 Generates Active MMP-2 Cancer Res., November 1, 2008; 68(21): 9096 - 9104. [Abstract] [Full Text] [PDF]

				D. V. Rozanov, A. Y. Savinov, R. Williams, K. Liu, V. S. Golubkov, S. Krajewski, and A. Y. Strongin Molecular Signature of MT1-MMP: Transactivation of the Downstream Universal Gene Network in Cancer Cancer Res., June 1, 2008; 68(11): 4086 - 4096. [Abstract] [Full Text] [PDF]

				Y. Itoh, N. Ito, H. Nagase, and M. Seiki The Second Dimer Interface of MT1-MMP, the Transmembrane Domain, Is Essential for ProMMP-2 Activation on the Cell Surface J. Biol. Chem., May 9, 2008; 283(19): 13053 - 13062. [Abstract] [Full Text] [PDF]

				T. Takino, H. Saeki, H. Miyamori, T. Kudo, and H. Sato Inhibition of Membrane-Type 1 Matrix Metalloproteinase at Cell-Matrix Adhesions Cancer Res., December 15, 2007; 67(24): 11621 - 11629. [Abstract] [Full Text] [PDF]

				S. D. Sithu, W. R. English, P. Olson, D. Krubasik, A. H. Baker, G. Murphy, and S. E. D'Souza Membrane-type 1-Matrix Metalloproteinase Regulates Intracellular Adhesion Molecule-1 (ICAM-1)-mediated Monocyte Transmigration J. Biol. Chem., August 24, 2007; 282(34): 25010 - 25019. [Abstract] [Full Text] [PDF]

				K. Sanka, R. Maddala, D. L. Epstein, and P. V. Rao Influence of Actin Cytoskeletal Integrity on Matrix Metalloproteinase-2 Activation in Cultured Human Trabecular Meshwork Cells Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2105 - 2114. [Abstract] [Full Text] [PDF]

				H. Piccard, P. E. Van den Steen, and G. Opdenakker Hemopexin domains as multifunctional liganding modules in matrix metalloproteinases and other proteins J. Leukoc. Biol., April 1, 2007; 81(4): 870 - 892. [Abstract] [Full Text] [PDF]

				M. A. Lafleur, F. A. Mercuri, N. Ruangpanit, M. Seiki, H. Sato, and E. W. Thompson Type I Collagen Abrogates the Clathrin-mediated Internalization of Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) via the MT1-MMP Hemopexin Domain J. Biol. Chem., March 10, 2006; 281(10): 6826 - 6840. [Abstract] [Full Text] [PDF]

				M. Kobel, G. Pohl, W. D. Schmitt, S. Hauptmann, T.-L. Wang, and I.-M. Shih Activation of Mitogen-Activated Protein Kinase Is Required for Migration and Invasion of Placental Site Trophoblastic Tumor Am. J. Pathol., September 1, 2005; 167(3): 879 - 885. [Abstract] [Full Text] [PDF]

				T. Nonaka, K. Nishibashi, Y. Itoh, I. Yana, and M. Seiki Competitive disruption of the tumor-promoting function of membrane type 1 matrix metalloproteinase/matrix metalloproteinase-14 in vivo Mol. Cancer Ther., August 1, 2005; 4(8): 1157 - 1166. [Abstract] [Full Text] [PDF]

				P. Osenkowski, S. O. Meroueh, D. Pavel, S. Mobashery, and R. Fridman Mutational and Structural Analyses of the Hinge Region of Membrane Type 1-Matrix Metalloproteinase and Enzyme Processing J. Biol. Chem., July 15, 2005; 280(28): 26160 - 26168. [Abstract] [Full Text] [PDF]

				K. Lehti, E. Allen, H. Birkedal-Hansen, K. Holmbeck, Y. Miyake, T.-H. Chun, and S. J. Weiss An MT1-MMP-PDGF receptor-{beta} axis regulates mural cell investment of the microvasculature Genes & Dev., April 15, 2005; 19(8): 979 - 991. [Abstract] [Full Text] [PDF]

				P. Wang, J. Nie, and D. Pei The Hemopexin Domain of Membrane-type Matrix Metalloproteinase-1 (MT1-MMP) Is Not Required for Its Activation of proMMP2 on Cell Surface but Is Essential for MT1-MMP-mediated Invasion in Three-dimensional Type I Collagen J. Biol. Chem., December 3, 2004; 279(49): 51148 - 51155. [Abstract] [Full Text] [PDF]

				H. G. Munshi, Y. I. Wu, S. Mukhopadhyay, A. J. Ottaviano, A. Sassano, J. E. Koblinski, L. C. Platanias, and M. S. Stack Differential Regulation of Membrane Type 1-Matrix Metalloproteinase Activity by ERK 1/2- and p38 MAPK-modulated Tissue Inhibitor of Metalloproteinases 2 Expression Controls Transforming Growth Factor-{beta}1-induced Pericellular Collagenolysis J. Biol. Chem., September 10, 2004; 279(37): 39042 - 39050. [Abstract] [Full Text] [PDF]