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Eps8 was initially identified as a substrate of the epidermal growth factorreceptor. Overexpression of Eps8 leads to increased mitogenic signaling and malignanttransformation. However, little is known concerning the importance of Eps8 inhuman gliomas. In this study, we found that Eps8 was overexpressed in 56.6% ofhuman gliomas (WHO grades III and IV) compared with adjacent normal brain tissuesby immunohistochemical analysis. The U251 human glioma cell line stably expressingEps8 was established by G418 screening, and the ectopic expression of Eps8 enhancedU251 glioma cell growth and survival by cell survival, MTT and liquid colony formationassays. By contrast, the lentiviral expression of Eps8 siRNA in SHG-44 cells resultedin a significant reduction in cellular growth and proliferation. Furthermore,Eps8 modulated the levels of phosphorylated extracellular signal-regulated proteinkinase (ERK), phosphorylated serine-threonine protein kinase Akt and β-cateninexpression in glioma cell lines and tissues. These results suggest that Eps8 isoverexpressed in human gliomas, and affects glioma cell growth possibly by regulatingERK and Akt/β-catenin signaling. Therefore, Eps8 may represent a novel potentialtarget in human glioma therapy.

Eps8 promotes cellular growth of human malignant gliomas