E-cadherin regulates the function of the EphA2 receptor tyrosine kinase

EphA2 is a member of the Eph family of receptor tyrosine kinases, which are increasingly understood to play critical roles in disease and development, We report here the regulation of EphA2 by E-cadherin. In nonneoplastic epi thelia, EphA2 was tyrosine-phosphorylated and localized to sites of cell-ce ll contact, These properties required the proper expression and functioning of E-cadherin. In breast cancer cells that lack E-cadherin, the phosphotyr osine content of EphA2 was decreased, and EphA2 was redistributed into memb rane ruffles, Expression of E-cadherin in metastatic cells restored a more normal pattern of EphA2 phosphorylation and localization. Activation of Eph A2, either by E-cadherin expression air antibody-mediated aggregation, decr eased cell-extracellular matrix adhesion and cell growth, Altogether, this demonstrates that EphA2 function is dependent on E-cadherin and suggests th at loss of E-cadherin function may alter neoplastic cell growth and adhesio n via effects on EphA2.