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Updated: Jun 14, 2026

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion
09:23

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion

Published on: April 2, 2020

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

Keren Borensztajn1, Maikel P Peppelenbosch, C Arnold Spek

  • 1Center for Experimental and Molecular Medicine, Academic Medical Center, Meibergdreef 9, NL-1105 AZ, Amsterdam, The Netherlands. K.S.Borensztajn@amc.uva.nl

Thrombosis Research
|March 30, 2010
PubMed

Insights

Activated coagulation factor X (FXa) inhibits cancer cell migration via protease-activated receptor 1 (PAR-1) signaling. This new research reveals FXa inactivates cofilin, stabilizing actin filaments and preventing cell movement.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Activated coagulation factor X (FXa) was previously shown to inhibit migration in breast, lung, and colon cancer cells.
  • The mechanism by which FXa influences cell migration, particularly the downstream signaling pathways, remained largely unknown.
  • FXa's role in cancer cell migration is mediated through protease-activated receptor 1 (PAR-1).

Purpose of the Study:

  • To elucidate the cellular signaling pathways involved in FXa-mediated inhibition of breast cancer cell migration.
  • To investigate the role of Rho/ROCK and Src/FAK/paxillin pathways in FXa's effect on cell motility.
  • To identify key molecular events leading to FXa-induced suppression of cancer cell invasion.

Main Methods:

  • Utilized specific inhibitors for ROCK and Src kinases to assess their role in FXa signaling.
  • Investigated downstream signaling events including myosin light chain phosphorylation, LIMK1 activation, and cofilin inactivation.
  • Employed gene knockdown of LIMK1 to determine its necessity for FXa-mediated inhibition of cell invasion.
  • Analyzed stress fiber formation and actin filament stabilization in response to FXa treatment.

Main Results:

  • Both Rho/ROCK and Src/FAK/paxillin pathways were identified as essential for FXa-induced inhibition of breast cancer cell migration.
  • FXa treatment led to significant stress fiber formation, partially mitigated by ROCK or Src inhibition.
  • FXa induced myosin light chain phosphorylation and LIMK1 activation, subsequently inactivating cofilin.
  • Knockdown of LIMK1 expression abrogated the FXa-induced inhibition of cancer cell invasion.
  • FXa promotes sustained cofilin inactivation, stabilizing actin filaments and hindering cell migration.

Conclusions:

  • FXa plays a significant role in regulating cancer cell migration beyond its hemostatic function.
  • A novel mechanism of PAR-1-mediated inhibition of cell migration involves FXa activating Rho and Src-dependent pathways.
  • Sustained inactivation of cofilin by FXa stabilizes actin cytoskeleton, rendering it incompatible with cell migration and invasion.

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