title: Membrane-type 1 matrix metalloproteinase regulates fibronectin assembly and N-cadherin adhesion.
abstract: Fibronectin matrix formation requires the increased cytoskeletal tension generated by cadherin adhesions, and is suppressed by membrane-type 1 matrix metalloproteinase (MT1-MMP). In a co-culture of Rat1 fibroblasts and MT1-MMP-silenced HT1080 cells, fibronectin fibrils extended from Rat1 to cell-matrix adhesions in HT1080 cells, and N-cadherin adhesions were formed between Rat1 and HT1080 cells. In control HT1080 cells contacting with Rat1 fibroblasts, cell-matrix adhesions were formed in the side away from Rat1 fibroblasts, and fibronectin assembly and N-cadherin adhesions were not formed. The role of N-cadherin adhesions in fibronectin matrix formation was studied using MT1-MMP-silenced HT1080 cells. MT1-MMP knockdown promoted fibronectin matrix assembly and N-cadherin adhesions in HT1080 cells, which was abrogated by double knockdown with either integrin β1 or fibronectin. Conversely, inhibition of N-cadherin adhesions by its knockdown or treatment with its neutralizing antibody suppressed fibronectin matrix formation in MT1-MMP-silenced cells. These results demonstrate that fibronectin assembly initiated by MT1-MMP knockdown results in increase of N-cadherin adhesions, which are prerequisite for further fibronectin matrix formation.
authors: Division of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. Electronic address: ttakino@staff.kanazawa-u.ac.jp.
authors: Takahisa
authors: T
authors: Takino
authors: Division of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan; Department of Oral and Maxillofacial Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
authors: Taisuke
authors: T
authors: Yoshimoto
authors: Department of Neurosurgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
authors: Mitsutoshi
authors: M
authors: Nakada
authors: Division of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors: Zichen
authors: Z
authors: Li
authors: Division of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors: Takahiro
authors: T
authors: Domoto
authors: Department of Oral and Maxillofacial Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
authors: Shuichi
authors: S
authors: Kawashiri
authors: Division of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. Electronic address: vhsato@staff.kanazawa-u.ac.jp.
authors: Hiroshi
authors: H
authors: Sato
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D021982:Cell-Matrix Junctions; D018920:Coculture Techniques; D005353:Fibronectins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*
chemical_list: D015820:Cadherins; D005353:Fibronectins; D053511:Matrix Metalloproteinase 14
keywords: Cell–matrix adhesion; Fibronectin; MT1-MMP; N-cadherin; Tumor