TY - JOUR
T1 - Ephrin-A1 is a negative regulator in glioma through down-reguation of EphA2 and FAK
AU - Liu, Dong Ping
AU - Wang, Yan
AU - Koeffler, H. Phillip
AU - Xie, Dong
PY - 2007/4
Y1 - 2007/4
N2 - 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 tumori-genesis 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.
AB - 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 tumori-genesis 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.
KW - EphA2
KW - Ephrin-A1
KW - FAK
KW - Gliomas
UR - http://www.scopus.com/inward/record.url?scp=34247860854&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34247860854&partnerID=8YFLogxK
U2 - 10.3892/ijo.30.4.865
DO - 10.3892/ijo.30.4.865
M3 - Article
C2 - 17332925
AN - SCOPUS:34247860854
SN - 1019-6439
VL - 30
SP - 865
EP - 871
JO - International journal of oncology
JF - International journal of oncology
IS - 4
ER -