O 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 Pevonedistat 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. Keywords: ENO1, NSCLC, Glycolysis, Cell proliferation, FAK/PI3K/AKT, EMTIntroduction Lung cancer arises from the bronchial mucosal epithelium and it is the leading cause of cancer mortality worldwide. Non-small cell lung cancer (NSCLC) is the most commonly diagnosed type of lung cancer, accounting for approximately 85 of all cases. Although the continuous progress has been made for surgical resection, chemotherapy, and* Correspondence: fangweiyi1975@163.com; narcissus_jane@163.com; songxin68@126.com Equal contributors 1 Cancer Center, Traditional Chinese Medicine-Integrated Hospital of Southern Medical University, Guangzhou, Guangdong, People's Republic China 2 Cancer Research Institute of Southern Medical University, Guangzhou, Guangdong, People's Republic China Full list of author information is available at the end of the articleradiation therapy [1-3], prognoses have not significant improved. In recent years, molecular targeted therapy [4,5] has become the most prevalent approach. Therefore, the understanding of the molecular alterations in NSCLC and their pathways is significant for molecular targeted therapy. During tumor formation and expansion, increasing glucose metabolism is necessary for the unrestricted growth of tumor cells [6]. Distributed in a variety of tissues, enolase (ENO1) was originally described as an enzyme responsible for the glycolytic pathway [7]. In addition to its glycolytic function, accumulating evidence has demonstrated that ENO1 is a multifunctional protein involved in several biological and pathophysiological processes depending on its cellular localization [8]. The PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/16989806 molecular?2015 Fu et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Fu et al. Journal of Hematology Oncology (2015)8:Page 2 ofweight of ENO1 protein is 48 kDa. It is expressed in the cytoplasm and considered as an oncogene in tumor pathogenesis. However, another transcript of ENO1 can be translated into a 37-kDa c-Myc promoter-binding protein (MBP-1), which represses transcription and is localized in the nucleus [9-11].