Alpha-enolase promotes cell glycolysis, growth, migration, and invasion in non-small cell lung cancer through FAK-mediated PI3K/AKT pathway

Journal of Hematology & Oncology

Xin Song¹  Zhen Liu⁴  Wei-Yi Fang²  Xiao-Jie Deng²  Li-Bo Li³  Rong Li³  Rong-Cheng Luo³  Yi-Yu Chen²  Xiao-Li Yu²  Yan Zhen²  Meng-Yang Zhao²  Rui-Lei Li¹  Su-Wei Dong²  Hong-Ying Qu³  Sheng-Ni Hua²  Yue Fan²  Yan Liu²  Qiao-Fen Fu² 

[1] Department of Cancer Biotherapy Center, Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, Yunnan, People’s Republic China;Cancer Research Institute of Southern Medical University, Guangzhou, Guangdong, People’s Republic China;Cancer Center, Traditional Chinese Medicine-Integrated Hospital of Southern Medical University, Guangzhou, Guangdong, People’s Republic China;Department of Pathology, Basic School of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic China

关键词: EMT;    FAK/PI3K/AKT;    Cell proliferation;    Glycolysis;    NSCLC;    ENO1;   

Others  :  1137537
DOI  :  10.1186/s13045-015-0117-5

 received in 2014-10-15, accepted in 2015-02-09,  发布年份 2015

【 摘 要 】

Background

During tumor formation and expansion, increasing glucose metabolism is necessary for unrestricted growth of tumor cells. Expression of key glycolytic enzyme alpha-enolase (ENO1) is controversial and its modulatory mechanisms are still unclear in non-small cell lung cancer (NSCLC).

Methods

The expression of ENO1 was examined in NSCLC and non-cancerous lung tissues, NSCLC cell lines, and immortalized human bronchial epithelial cell (HBE) by quantitative real-time reverse transcription PCR (qRT-PCR), immunohistochemistry, and Western blot, respectively. The effects and modulatory mechanisms of ENO1 on cell glycolysis, growth, migration, invasion, and in vivo tumorigenesis and metastasis in nude mice were also analyzed.

Results

ENO1 expression was increased in NSCLC tissues in comparison to non-cancerous lung tissues. Similarly, NSCLC cell lines A549 and SPCA-1 also express higher ENO1 than HBE cell line in both mRNA and protein levels. Overexpressed ENO1 significantly elevated NSCLC cell glycolysis, proliferation, clone formation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo by regulating the expression of glycolysis, cell cycle, and epithelial-mesenchymal transition (EMT)-associated genes. Conversely, ENO1 knockdown reversed these effects. More importantly, our further study revealed that stably upregulated ENO1 activated FAK/PI3K/AKT and its downstream signals to regulate the glycolysis, cell cycle, and EMT-associated genes.

Conclusion

This study showed that ENO1 is responsible for NSCLC proliferation and metastasis; thus, ENO1 might serve as a potential molecular therapeutic target for NSCLC treatment.

【 授权许可】

   
2015 Fu et al.; licensee BioMed Central.

【 图 表 】

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