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Biochem Biophys Res Commun. 2013 Jul 5;436(3):503-8. doi: 10.1016/j.bbrc.2013.05.134. Epub 2013 Jun 10.

MT1-MMP prevents growth inhibition by three dimensional fibronectin matrix.

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  • 1Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. ttakino@staff.kanazawa-u.ac.jp


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.

Copyright © 2013 Elsevier Inc. All rights reserved.


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

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