c-Jun N-terminal kinase is involved in motility of endothelial cell

E Y Shin1, S Y Kim, E G Kim

  • 1Department of Biochemistry, College of Medicine, Chungbuk National University, Medical Research Institute and Research Institute for Genetic Engineering, Cheongju, Korea.

Insights

The Ras-SEK1-JNK pathway is crucial for endothelial cell motility and angiogenesis. Inhibiting JNK significantly reduces cell migration, highlighting its role in these processes.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Cell motility is vital for angiogenesis and tumor metastasis.
  • Ras proteins are involved in cell migration and invasion, upstream of MAPK pathways.
  • The specific role of c-Jun N-terminal kinase (JNK) in endothelial cell motility requires further investigation.

Purpose of the Study:

  • To investigate the role of JNK in endothelial cell motility.
  • To determine if the Ras-SEK1-JNK pathway regulates endothelial cell migration during angiogenesis.

Main Methods:

  • Utilized stable transfectants (DAR-ECV) of ECV304 endothelial cells expressing oncogenic H-Ras.
  • Assessed cell motility and angiogenic potential using Western blot analysis.
  • Examined the effects of JNK inhibitors (curcumin, all trans-retinoic acid) and JNK agonists (TNFalpha, anisomycin).
  • Generated ECV304 cells expressing dominant active SEK1 (DAS-ECV) to confirm JNK pathway activation.

Main Results:

  • DAR-ECV cells exhibited a two-fold increase in angiogenic potential and motility compared to control ECV304 cells.
  • Constitutive JNK activation was observed in DAR-ECV cells.
  • JNK inhibitors dose-dependently decreased basal and agonist-stimulated motility of DAR-ECV cells.
  • Enhanced basal cell migration was observed in DAS-ECV cells, indicating JNK pathway involvement.

Conclusions:

  • The Ras-SEK1-JNK signaling pathway plays a significant role in regulating endothelial cell motility.
  • This pathway is a key regulator of endothelial cell behavior during angiogenesis.
  • Targeting the JNK pathway may offer therapeutic strategies for angiogenesis-related diseases.

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