title: Ephrin-A1 is a negative regulator in glioma through down-regulation of EphA2 and FAK.
abstract: Eph receptors, the largest receptor tyrosine kinases, and their ephrin ligands play important roles in axon guidance and cell migration during development of the nervous system. Recently, these molecules are also found involved in tumorigenesis of different kinds of cancers. In this study, we demonstrated that expression of ephrin-A1 was dramatically down-regulated in glioma cell lines and in primary gliomas compared to the matched normal tissues. Forced expression of ephrin-A1 attenuated cell migration, cell proliferation, and adhesion-independent growth in human glioma U251 cells. EphA2, a receptor for ephrin-A1 and an oncoprotein, was greatly decreased in ephrin-A1-transfected glioma cells. Overexpression of ephrin-A1 stimulated activation of EphA2 by phosphorylation and led to its degradation. Furthermore, focal adhesion kinase (FAK), a known downstream molecule of EphA2, was also down-regulated in the ephrin-A1 transfected cells. These results suggested that ephrin-A1 serves as a critical negative regulator in the tumorigenesis of gliomas by down-regulating EphA2 and FAK, which may provide potential valuable targets for therapeutic intervention.
authors.affiliation: Laboratory of Molecular Oncology, Institute for Nutritional Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, P.R. China.
authors.forename: Dong-Ping
authors.initials: DP
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: H Phillip
authors.initials: HP
authors.lastname: Koeffler
authors.forename: Dong
authors.initials: D
authors.lastname: Xie
mesh_terms: D001932:Brain Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D015536:Down-Regulation; D036382:Ephrin-A1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D036383:Ephrin-A2 / Q000032:analysis / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D005910:Glioma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D014407:Tumor Cells, Cultured
chemical_list: D036382:Ephrin-A1; D036383:Ephrin-A2; D051416:Focal Adhesion Protein-Tyrosine Kinases