Publication

Coagulation Factor Xa inhibits cancer cell migration via LIMK1-mediated cofilin inactivation

Borensztajn, K., Peppelenbosch, M. P. & Spek, C. A., Jun-2010, In : Thrombosis Research. 125, 6, p. E323-E328 6 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Keren Borensztajn
  • Maikel P. Peppelenbosch
  • C. Arnold Spek

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. laments 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. (C) 2010 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)E323-E328
Number of pages6
JournalThrombosis Research
Volume125
Issue number6
Publication statusPublished - Jun-2010

    Keywords

  • Coagulation factor Xa, Cancer cell, Cell migration, Protease activated receptor, Signaling, MEDIATED TYROSINE PHOSPHORYLATION, PROTEASE-ACTIVATED RECEPTOR-2, FOCAL ADHESION KINASE, TUMOR-CELLS, SPHINGOSINE 1-PHOSPHATE, DIFFERENTIAL REGULATION, COUPLED RECEPTOR, CARCINOMA CELLS, FACTOR-VIIA, LIM KINASE

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