title: E-cadherin regulates the function of the EphA2 receptor tyrosine kinase.
abstract: 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 epithelia, EphA2 was tyrosine-phosphorylated and localized to sites of cell-cell contact. These properties required the proper expression and functioning of E-cadherin. In breast cancer cells that lack E-cadherin, the phosphotyrosine content of EphA2 was decreased, and EphA2 was redistributed into membrane ruffles. Expression of E-cadherin in metastatic cells restored a more normal pattern of EphA2 phosphorylation and localization. Activation of EphA2, either by E-cadherin expression or antibody-mediated aggregation, decreased cell-extracellular matrix adhesion and cell growth. Altogether, this demonstrates that EphA2 function is dependent on E-cadherin and suggests that loss of E-cadherin function may alter neoplastic cell growth and adhesion via effects on EphA2.
authors.affiliation: Department of Basic Medical Sciences and Purdue Cancer Center, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: N D
authors.initials: ND
authors.lastname: Zantek
authors.forename: M
authors.initials: M
authors.lastname: Azimi
authors.forename: M
authors.initials: M
authors.lastname: Fedor-Chaiken
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Brackenbury
authors.forename: M S
authors.initials: MS
authors.lastname: Kinch
mesh_terms: D001943:Breast Neoplasms; D015820:Cadherins / Q000032:analysis / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D036383:Ephrin-A2; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D006801:Humans; D010766:Phosphorylation; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
chemical_list: D015820:Cadherins; D036383:Ephrin-A2; D014157:Transcription Factors; D014443:Tyrosine