Ligation of EphA2 by Ephrin A1-Fc inhibits pancreatic adenocarcinoma cellular invasiveness.
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.
Duxbury
Mark S
MS
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. duxbury@doctors.org.uk
Ito
Hiromichi
H
Zinner
Michael J
MJ
Ashley
Stanley W
SW
Whang
Edward E
EE
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*
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