Presentation Abstract

Abstract Number: 5216
Presentation Title: An Akt-EphA2 reciprocal regulatory loop controls tumor cell migration and invasion
Presentation Time: Wednesday, Apr 21, 2010, 8:00 AM -11:00 AM
Location: Exhibit Hall A-C, Poster Section 14
Poster Section: 14
Poster Board Number: 30
Author Block: Hui Miao, Hong Guo, Aaron Petty, Andrew Sloan, David Danielpour, James Basilion, Jennifer Cutter, John Sedor, Mark Cohen, Amitava Mukherjee, Bingcheng Wang. Case Western Reserve Univ., Cleveland, OH
Abstract Body: EphA2 is a member of Eph family receptor tyrosine kinases that has been implicated in many types of human cancers. Perplexingly, both pro- and anti-oncogenic properties have been attributed to EphA2 kinase. We report here that a possible cause for this apparent paradox is diametrically opposite roles of EphA2 in regulating cell migration and invasion. While activation of EphA2 with its ligand ephrin-A1 inhibited chemotactic migration of glioma and prostate cancer cells, EphA2 overexpression promoted migration in a ligand-independent manner. Surprisingly, the latter effects required phosphorylation of EphA2 on serine 897 by Akt, and S897A mutation abolished ligand-independent promotion of cell motility. Ephrin-A1 stimulation of EphA2 negated Akt activation by growth factors and caused EphA2 dephosphorylation on S897. In human astrocytoma, S897 phosphorylation was correlated with tumor grades and Akt activation, suggesting that the Akt-EphA2 crosstalk may contribute to brain tumor progression.