The HGF/SF-induced phosphorylation of paxillin, matrix adhesion, and invasion of prostate cancer cells were suppressed by NK4, an HGF/SF variant

Biochem Biophys Res Commun. 2001 Aug 3;285(5):1330-7. doi: 10.1006/bbrc.2001.5307.

Abstract

Hepatocyte growth factor/scatter factor (HGF/SF) plays a crucial role in cancer cell migration, matrix adhesion, invasion, and angiogenesis, via the phosphorylation of the c-met tyrosine kinase. This study examined the ability of NK4, a recently discovered HGF/SF variant, to inhibit the influence of HGF/SF on cell-matrix interaction, paxillin phosphorylation, and invasion of prostate cancer cells. HGF/SF was shown to dramatically enhance tumour cell motility, invasion, cell-matrix adhesion, together with an increase in the degree of paxillin phosphorylation and formation of focal adhesion complexes. However, these HGF/SF-induced effects were suppressed by the presence of NK4. NK4 effectively inhibited the degree of HGF/SF-induced paxillin phosphorylation and matrix adhesion. As a consequence, the matrix invasion of these prostate cancer cells was also suppressed by NK4. In conclusion, this study shows that these HGF/SF-enhanced events, which are critical steps in metastasis, can be inhibited through the addition of NK4, thus warranting further in vivo studies on the implication of NK4 as a potential antimetastasis agent in prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Blotting, Western
  • Cell Adhesion / drug effects
  • Cell Division / drug effects
  • Cell Movement / drug effects*
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / metabolism*
  • Extracellular Matrix / metabolism*
  • Fluorescent Antibody Technique
  • Hepatocyte Growth Factor / antagonists & inhibitors
  • Hepatocyte Growth Factor / pharmacology*
  • Humans
  • Male
  • Mitogens*
  • Neoplasm Invasiveness
  • Paxillin
  • Phosphoproteins / analysis
  • Phosphoproteins / metabolism*
  • Phosphorylation / drug effects
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Tumor Cells, Cultured
  • Tyrosine / metabolism

Substances

  • Antineoplastic Agents
  • Cytoskeletal Proteins
  • HGF protein, human
  • Mitogens
  • PXN protein, human
  • Paxillin
  • Phosphoproteins
  • Tyrosine
  • Hepatocyte Growth Factor