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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / metabolism*
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Adenocarcinoma / pathology*
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Cell Division / drug effects
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Cell Line, Tumor / drug effects
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Cell Line, Tumor / metabolism
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Cell Line, Tumor / pathology
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Cell Movement / drug effects
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Ephrin-A1
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Focal Adhesion Kinase 1
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Focal Adhesion Protein-Tyrosine Kinases
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Humans
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Immunoglobulin Fc Fragments
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Matrix Metalloproteinase 2 / metabolism*
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Pancreatic Neoplasms / metabolism*
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Pancreatic Neoplasms / pathology*
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Protein-Tyrosine Kinases / metabolism*
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Receptor, EphA2 / antagonists & inhibitors
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Receptor, EphA2 / metabolism*
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Recombinant Fusion Proteins / pharmacology*
Substances
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Ephrin-A1
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Immunoglobulin Fc Fragments
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Recombinant Fusion Proteins
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ephrin A1-Fc fusion protein, recombinant
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Protein-Tyrosine Kinases
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Receptor, EphA2
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Focal Adhesion Kinase 1
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Focal Adhesion Protein-Tyrosine Kinases
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PTK2 protein, human
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Matrix Metalloproteinase 2