title: Membrane-type 1 matrix metalloproteinase regulates fibronectin assembly to promote cell motility.
abstract: Fibronectin (FN) matrix assembly is an essential process in normal vertebrate development, which is frequently lost in tumor cells. Here we show that membrane-type 1 matrix metalloproteinase (MT1-MMP) regulates FN matrix assembly. MT1-MMP knockdown induced FN assembly in breast carcinoma cells. Ectopic expression of MT1-MMP reduced specifically the assembled FN matrix level without affecting whole FN production in fibroblasts. Treatment of fibrosarcoma HT1080 cells with dexamethasone (DEX) enhanced FN synthesis, resulting in short fibrils but not dense matrix formation. Combined treatment of DEX and MT1-MMP inhibitor accelerated FN matrix assembly, which mediated cellular adhesion and reduced cell migration and invasion. These results indicate that MT1-MMP stimulates cell migration and invasion by negatively regulating FN assembly.
authors: Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. ttakino@kenroku.kanazawa-u.ac.jp
authors: Takahisa
authors: T
authors: Takino
authors: Ryota
authors: R
authors: Nagao
authors: Ri-ichiroh
authors: R
authors: Manabe
authors: Takahiro
authors: T
authors: Domoto
authors: Kiyotoshi
authors: K
authors: Sekiguchi
authors: Hiroshi
authors: H
authors: Sato
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D005353:Fibronectins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D051381:Rats; D013379:Substrate Specificity
chemical_list: D005353:Fibronectins; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D053511:Matrix Metalloproteinase 14