MT1-MMP promotes cell growth and ERK activation through c-Src and paxillin in three-dimensional collagen matrix

フォーマット:

論文

責任表示:

Takino, Takahisa ; Tsuge, Hisashi ; Ozawa, Terumasa ; Sato, Hiroshi

言語:

英語

出版情報:

Elsevier, 2010-06-01

著者名:

• Takino, Takahisa
• Tsuge, Hisashi
• Ozawa, Terumasa
• Sato, Hiroshi

掲載情報:

Biochemical and Biophysical Research Communications

ISSN:

0006-291x      

巻:

396

通号:

4

開始ページ:

1042

終了ページ:

1047

バージョン:

author

概要:

金沢大学がん研究所<br />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 collage … n 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. 続きを見る

URL:

http://hdl.handle.net/2297/24574