Résumé
The erythropoietin-producing hepatocellular receptor (Eph) and its ligand ephrin are the largest of the receptor tyrosine kinases (RTKs) family in humans. Since ephrin ligands and Eph receptors are membrane-bound proteins, binding and activation of Eph/ephrin intracellular signaling pathways can only occur via direct cell-cell interaction. Eph-ephrin complexes emanate bidirectional signals that affect cells expressing Eph and ephrin, respectively. Its repulsive signaling effects include retraction, which plays an important role in many physiological and pathological processes. EphA2 has been found to have a strong association with tumors and is most widely studied. EphA2 signal transduction in tumor cells may promote or inhibit tumor, depending on the tumor microenvironment. EphA2 "canonical" signaling involves ligand binding and kinase activity; thus EphA2 "noncanonical" signaling is ligand independent and lacks kinase activity. This review summarizes the pathogenesis of EphA2 in nasopharyngeal carcinoma (NPC), including ligand independent signal and EBV infection receptor, furthermore evaluates the prospect of its potential utilization as a target for cancer therapeutics. This may provide a new method for the prevention and treatment of NPC.
Résumé
AIM:To investigate the effect of Eph receptor A2 (EphA2) on drug resistance of colorectal carci-noma cells and its possible mechanisms .METHODS:Real-time PCR and Western blot were used to detect the expression of EphA2 at mRNA and protein levels in LoVo and LoVo/5-FU cells.EphA2 siRNA was transfected to down-regulate the EphA2 expression in LoVo/5-FU cells, and the drug sensitivity was calculated by CCK-8 assay.Meanwhile, cell migration and invasion were measured by wound healing assay and Transwell assay , and the protein levels of E-cadherin,β-catenin, N-cadherin, vimentin, Notch and Snail were determined by Western blot .RESULTS: The expression of EphA2 at both mRNA and protein levels was significantly up-regulated in LoVo/5-FU cells (P<0.05).Knockdown of EphA2 suppressed the cell viability, and migration and invasion abilities , but promoted drug sensitivity of LoVo/5-FU cells.Up-regulation of E-cadherin and β-catenin, and down-regulation of N-cadherin and vimentin were observed , indicating that the epithelial-mesenchymal transition ( EMT) process was suppressed .Knockdown of EphA2 decreased the expression levels of Notch and Snail.CONCLUSION:Down-regulation of EphA2 partly reverses drug resistance of LoVo/5-FU cells.The mechanism may be related to suppressing cell growth , migration, invasion and EMT process via Notch/Snail signaling pathway .