title: MT1-MMP prevents growth inhibition by three dimensional fibronectin matrix.
abstract: The extracellular microenvironment plays a key role in regulation of cellular functions and growth control. We show here that membrane-type 1 matrix metalloproteinase (MT1-MMP) acts as a growth promoter in confluent culture. When MT1-MMP was silenced in HT1080 fibrosarcoma cells, cells created three dimensional (3D) fibronectin matrix in a confluent culture, and growth of cells embedded within it was retarded. Formation of 3D fibronectin matrix initiated by MT1-MMP silencing was impeded by knockdown of either FN or integrin β₁, which resulted in restoration of cell growth. When cells in 3D fibronectin matrix were treated with integrin β₁ inhibitory antibody, cells underwent S phase entry. These results suggest that MT1-MMP prevents growth suppression by 3D fibronectin matrix, which is mediated through integrin β₁.
authors.affiliation: Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. ttakino@staff.kanazawa-u.ac.jp
authors.forename: Takahisa
authors.initials: T
authors.lastname: Takino
authors.forename: Luyang
authors.initials: L
authors.lastname: Guo
authors.forename: Takahiro
authors.initials: T
authors.lastname: Domoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D005354:Fibrosarcoma / Q000201:enzymology / Q000378:metabolism; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016196:S Phase
chemical_list: D005353:Fibronectins; D019012:Integrin beta1; D034741:RNA, Small Interfering; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14
keywords: 3D; DMEM; Dulbecco’s modified Eagle’s medium; ECM; ERK; FN; Growth; Integrin; MAPK; MMP; MT1-MMP; PBS; Tumor; extracellular matrix; extracellular signal-regulated kinase; fibronectin; matrix metalloproteinase; membrane-type 1 MMP; mitogen-activated protein kinase; pRb; phosphate-buffered saline; retinoblastoma protein; siRNA; small interfering RNA; three-dimensional