کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1932075 | 1050572 | 2010 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: MT1-MMP promotes cell growth and ERK activation through c-Src and paxillin in three-dimensional collagen matrix MT1-MMP promotes cell growth and ERK activation through c-Src and paxillin in three-dimensional collagen matrix](/preview/png/1932075.png)
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.
Journal: Biochemical and Biophysical Research Communications - Volume 396, Issue 4, 11 June 2010, Pages 1042–1047