Ligation of EphA2 by Ephrin A1-Fc Inhibits Pancreatic Adenocarcinoma Cellular Invasiveness

Biochem Biophys Res Commun. 2004 Aug 6;320(4):1096-102. doi: 10.1016/j.bbrc.2004.06.054.

Abstract

The Eph tyrosine kinases interact with ligands of the Ephrin family and have diverse cellular functions. EphA2 has been recognized to be an oncoprotein of importance in a range of cancers. Here, we examine the effect of EphA2 overexpression and ligation by chimeric Ephrin A1-Fc on the invasive phenotype of pancreatic adenocarcinoma cells. We show that EphA2 overexpression induces a FAK-dependent increase in MMP-2 expression and invasiveness. EphA2 ligation induces proteosomal degradation of EphA2, attenuates the invasive phenotype, and decreases both FAK phosphorylation and MMP-2 expression. EphA2 appears to represent a rational therapeutic target and ligation by Ephrin A1-Fc is one strategy to modulate levels of this oncoprotein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Cell Division / drug effects
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / metabolism
  • Cell Line, Tumor / pathology
  • Cell Movement / drug effects
  • Ephrin-A1
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Humans
  • Immunoglobulin Fc Fragments
  • Matrix Metalloproteinase 2 / metabolism*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology*
  • Protein-Tyrosine Kinases / metabolism*
  • Receptor, EphA2 / antagonists & inhibitors
  • Receptor, EphA2 / metabolism*
  • Recombinant Fusion Proteins / pharmacology*

Substances

  • Ephrin-A1
  • Immunoglobulin Fc Fragments
  • Recombinant Fusion Proteins
  • ephrin A1-Fc fusion protein, recombinant
  • Protein-Tyrosine Kinases
  • Receptor, EphA2
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTK2 protein, human
  • Matrix Metalloproteinase 2