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Background: The success of using glycolytic inhibitors for cancer treatment relies on studying the individual roles of frequently deregulated glycolytic genes in cancer.This report analyzed the involvement of a key glycolytic enzyme,alpha-enolase (ENO1) in tumor progression and prognosis of human glioma.Methods: ENO 1 expression levels were examined in glioma tissues and normal brain (NB) tissues.The effects and molecular mechanisms of ENO1 expression on cell growth,migration and invasion were also explored separately by MTT assay,transwell chamber assay,boyden chamber assay,western blot and in vivo tumorigenesis in nude mice.Results: ENO1 was observed to be downregulated in NB compared to glioma tissues at the mRNA and protein levels.Furthermore,increased ENO 1 was associated disease progression of glioma samples.Knocking down ENO1 expression not only significantly decreased cell proliferation,but also markedly inhibited the ability of cell migration and invasion as well as in vivo tumorigenesis.Mechanistic analysis revealed that Cyclin D1,Cyelin El,pRb,and NF-κB were downregulated after stable ENO1 knockdown in glioma U251 and U87 cells,while knockdown of ENO1 resulted in restoration of E-cadherin expression and suppression of mesenchymal cell markers such as Vimentin,Snail,N-Cadherir,β-Catenin and Slug.Futhermore,ENO1 suppression inactivated PI3K/Akt pathway regulating the cell growth and epithelial-mesenchymal transition (EMT) progression.Conclusion: Overexpression of ENO1 is an unfavorable factor which may facilitate glioma progression.Knockdown ENO1 expression led to suppressed cell growth,migration and invasion progression by activating the PI3K/Akt pathway in glioma cells.