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Echistatin induces decrease of pp125FAK phosphorylation, disassembly of actin cytoskeleton and focal adhesions, and detachment of fibronectin-adherent melanoma cells.

Abstract
B16-BL6 mouse melanoma cells cultured on fibronectin-coated dishes were detached by treatment with echistatin, an RGD-containing disintegrin. Echistatin was active at micromolar concentrations and was not cytotoxic. Its effect was dose-dependent and reversible. Sequential morphological changes leading to rounding up of the cells were detected by phase-contrast microscopy and by immunofluorescence analysis. A dramatic reduction in the number and size of focal adhesions and loss of cytoplasmic actin filaments were observed well before cell detachment occurred. Echistatin treatment down-regulated the phosphorylation of pp125FAK in fibronectin-adherent cells in a dose- and time-dependent fashion. The reduction of pp125FAK phosphorylation preceded cell detachment and occurred even in the presence of orthovanadate, an inhibitor of protein tyrosine phosphatases. These results suggest that echistatin detaches cells from the fibronectin substratum by inducing a decrease of pp125FAK phosphorylation and that echistatin acts by inhibiting protein tyrosine kinase activity rather than activating protein tyrosine phosphatases.
AuthorsN Staiano, C Garbi, C Squillacioti, S Esposito, E Di Martino, M A Belisario, L Nitsch, P Di Natale
JournalEuropean journal of cell biology (Eur J Cell Biol) Vol. 73 Issue 4 Pg. 298-305 (Aug 1997) ISSN: 0171-9335 [Print] GERMANY
PMID9270872 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Actins
  • Cell Adhesion Molecules
  • Enzyme Inhibitors
  • Fibronectins
  • Peptides
  • Viper Venoms
  • echistatin
  • Phosphotyrosine
  • Vanadates
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Ptk2 protein, mouse
  • Protein Tyrosine Phosphatases
Topics
  • Actin Cytoskeleton (drug effects)
  • Actins (drug effects)
  • Animals
  • Cell Adhesion (drug effects)
  • Cell Adhesion Molecules (chemistry, metabolism)
  • Cell Membrane (drug effects)
  • Enzyme Inhibitors (pharmacology)
  • Fibronectins (metabolism)
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Melanoma
  • Mice
  • Peptides (pharmacology)
  • Phosphorylation
  • Phosphotyrosine (analysis)
  • Protein Tyrosine Phosphatases (antagonists & inhibitors)
  • Protein-Tyrosine Kinases (antagonists & inhibitors, chemistry, metabolism)
  • Tumor Cells, Cultured
  • Vanadates (pharmacology)
  • Viper Venoms (pharmacology)

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