Alpha-enolase as a potential cancer prognostic marker promotes cell growth, migration, and invasion in glioma

Ye Song,Songtao Qi,Tianshi Que,Hao Long,Qisheng Luo,Liu Yi,Zhiyong Li,Zhen Liu,Zheng Hu,Gang Wang,Xi’An Zhang,Weiyi Fang

doi:10.1186/1476-4598-13-65

Abstract

BackgroundThe success of using glycolytic inhibitors for cancer treatment relies on better understanding the roles of each 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.MethodsENO1 expression levels were examined in glioma tissues and normal brain (NB) tissues. The molecular mechanisms of ENO1 expression and its effects on cell growth, migration and invasion were also explored by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, Transwell chamber assay, Boyden chamber assay, Western blot and in vivo tumorigenesis in nude mice.ResultsENO1 mRNA and protein levels were upregulated in glioma tissues compared to NB. In addition, increased ENO1 was associated disease progression in glioma samples. Knocking down ENO1 expression not only significantly decreased cell proliferation, but also markedly inhibited cell migration and invasion as well as in vivo tumorigenesis. Mechanistic analyses revealed that Cyclin D1, Cyclin E1, pRb, and NF-κB were downregulated after stable ENO1 knockdown in glioma U251 and U87 cells. Conversely, knockdown of ENO1 resulted in restoration of E-cadherin expression and suppression of mesenchymal cell markers, such as Vimentin, Snail, N-Cadherin, β-Catenin and Slug. Furthermore, ENO1 suppression inactivated PI3K/Akt pathway regulating the cell growth and epithelial-mesenchymal transition (EMT) progression.ConclusionOverexpression of ENO1 is associated with glioma progression. Knockdown of ENO1 expression led to suppressed cell growth, migration and invasion progression by inactivating the PI3K/Akt pathway in glioma cells.

Highlights

The success of using glycolytic inhibitors for cancer treatment relies on better understanding the roles of each frequently deregulated glycolytic genes in cancer
Expression of ENO1 gene in glioma and normal brain (NB) tissues In order to assess the role of ENO1 in glioma, we performed real-time PCR to measure the expression of ENO1 mRNA transcripts in 45 freshly collected glioma tissues and 15 freshly collected NB tissues
We found no significant association between ENO1 expression levels and patients’ age, sex or histologic type in the 136 glioma cases

Summary

Introduction

The success of using glycolytic inhibitors for cancer treatment relies on better understanding the roles of each 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. Malignant gliomas account for the vast majority of adult malignant brain tumors that are graded according to the WHO classification system, which has implications for prognosis and management [1]. Malignant glioma cells thrive despite an irregular blood supply and frequently in a hypoxic microenvironment [5]. Compensatory mechanisms, including glucose uptake and glycolytic activity, are increased in these tumors [6]. Recent studies indicated that some glycolytic enzymes are complicated, multifaceted proteins rather than simple components of the glycolytic pathway [7]

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