کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3027696 1182986 2010 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Coagulation Factor Xa inhibits cancer cell migration via LIMK1-mediated cofilin inactivation
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Coagulation Factor Xa inhibits cancer cell migration via LIMK1-mediated cofilin inactivation
چکیده انگلیسی

Previously, we showed that activated coagulation factor X (FXa) inhibits migration of breast, lung and colon cancer cells. We showed that the effect of FXa on migration was protease-activated receptor (PAR)-1-dependent, but the subsequent cellular signaling routes remained elusive. In the current manuscript, we show that both the Rho/ROCK and Src/FAK/paxillin pathways are required for FXa-mediated inhibition of breast cancer cell migration. FXa induced pronounced stress fiber formation that was partially inhibited by pre-treatment with specific ROCK or Src inhibitors. Downstream of Rho/ROCK and Src/FAK/paxillin, FXa induced myosin light chain phosphorylation and LIMK1 activation resulting in cofilin inactivation. Knocking-down LIMK1 expression abolished FXa-induced inhibition of cell invasion. Our results reveal that FXa-mediated sustained cofilin inactivation leads to stabilization of actin filaments incompatible with migration. Overall we confirm that, beyond its role in blood coagulation, FXa plays a key role in cell migration and we unravel a new mechanism of PAR-1-mediated inhibition of migration via Rho and Src dependent pathways.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Thrombosis Research - Volume 125, Issue 6, June 2010, Pages e323–e328
نویسندگان
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