title: Ligation of EphA2 by Ephrin A1-Fc inhibits pancreatic adenocarcinoma cellular invasiveness.
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.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. duxbury@doctors.org.uk
authors.forename: Mark S
authors.initials: MS
authors.lastname: Duxbury
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ito
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zinner
authors.forename: Stanley W
authors.initials: SW
authors.lastname: Ashley
authors.forename: Edward E
authors.initials: EE
authors.lastname: Whang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D036382:Ephrin-A1; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D007141:Immunoglobulin Fc Fragments; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D036104:Receptor, EphA2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*
chemical_list: D036382:Ephrin-A1; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; C489246:ephrin A1-Fc fusion protein, recombinant; D011505:Protein-Tyrosine Kinases; D036104:Receptor, EphA2; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D020778:Matrix Metalloproteinase 2