کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2178869 1549754 2008 16 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Focal adhesion kinase mediates defects in the force-dependent reinforcement of initial integrin–cytoskeleton linkages in metastatic colon cancer cell lines
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک دانش گیاه شناسی
پیش نمایش صفحه اول مقاله
Focal adhesion kinase mediates defects in the force-dependent reinforcement of initial integrin–cytoskeleton linkages in metastatic colon cancer cell lines
چکیده انگلیسی

Micro-environmental clues, including the biophysical interpretation of the extracellular matrix, are critical to proliferation, apoptosis and migration. Here, we show that metastatic human colon cancer cell lines display altered matrix interaction. Interaction of colon cancer cells with collagen I depends on integrins (mainly α1/β1) but metastatic cells display delayed spreading and reduced extension of lamellipodia. In addition, cells show defective strengthening of integrin–cytoskeleton linkages upon mechanical stimulation, as determined by laser trapping experiments and binding of large beads to the cell surface. However, adhesion to pliable surfaces is ameliorated in metastatic variants. These changes are caused by constitutive activation of focal adhesion kinase (FAK) and can be modulated by changing expression and/or activity of FAK via RNA-interference or expression of inhibitory constructs, respectively. In addition, consistent with defective strengthening of integrin–cytoskeleton linkages, metastatic cell lines show reduced random motility. Taken together these data suggest that constitutive activation of FAK causes defects in spreading, reinforcement of integrin–cytoskeleton linkages and migration and at the same time could ameliorate the adhesion of metastatic cells to suboptimal surfaces.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Cell Biology - Volume 87, Issue 1, 15 January 2008, Pages 1–16
نویسندگان
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