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タイトル: MT1-MMP promotes cell growth and ERK activation through c-Src and paxillin in three-dimensional collagen matrix
著者: Takino, Takahisa link image link image
Tsuge, Hisashi
Ozawa, Terumasa
Sato, Hiroshi link image
滝野, 隆久
佐藤, 博
発行日: 2010年 6月
出版社(者): Elsevier
雑誌名: Biochemical and Biophysical Research Communications
ISSN: 0006-291X
巻: 396
号: 4
開始ページ: 1042
終了ページ: 1047
キーワード: Cancer
ECM
Growth
Integrin
MAPK
MT1-MMP
抄録: Membrane-type 1 matrix metalloproteinase (MT1-MMP) is essential for tumor invasion and growth. We show here that MT1-MMP induces extracellular signal-regulated kinase (ERK) activation in cancer cells cultured in collagen gel, which is indispensable for their proliferation. Inhibition of MT1-MMP by MMP inhibitor or small interfering RNA suppressed activation of focal adhesion kinase (FAK) and ERK in MT1-MMP-expressing cancer cells, which resulted in up-regulation of p21WAF1 and suppression of cell growth in collagen gel. Cell proliferation was also abrogated by the inhibitor against ERK pathway without affecting FAK phosphorylation. MT1-MMP and integrin αvβ3 were shown to be involved in c-Src activation, which induced FAK and ERK activation in collagen gel. These MT1-MMP-mediated signal transductions were paxillin dependent, as knockdown of paxillin reduced cell growth and ERK activation, and co-expression of MT1-MMP with paxillin induced ERK activation. The results suggest that MT1-MMP contributes to proliferation of cancer cells in the extracellular matrix by activating ERK through c-Src and paxillin. © 2010 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.bbrc.2010.05.059
URI: http://hdl.handle.net/2297/24574
関連URI: http://www.elsevier.com/locate/issn/0006291X
資料種別: Journal Article
版表示: author
出現コレクション:1. 査読済論文

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