Enolase transforms 2-phospho-D-glycerate into
phosphoenolpyruvate during glycolysis. The human
enolase (ENO) family comprises three members named ENO3, which is restricted to muscle tissues, ENO2, which is neuron- and neuroendocrine tissue-specific, and ENO1, which is expressed in almost all tissues. ENO1 is involved in various types of human
cancer, including
retinoblastoma,
hepatocellular carcinoma,
pancreatic cancer,
renal cell carcinoma,
cholangiocarcinoma and
gastric cancer. Furthermore, ENO1 enhances cell transformation in numerous
cancer cell lines. It has been reported that ENO1 is involved in various activities that are detrimental to cell transformation, including apoptosis and differentiation. However, a few studies demonstrated that ENO1 can be down- or upregulated in various types of
lung cancer, which suggests that ENO1 has an ambiguous role in the development of
lung cancer. The present study aimed to investigate the differential influences of ENO1 on various types of
cancer, and to clarify the role of ENO1 in
lung cancer in particular. Western blotting was performed to assess ENO1
protein expression levels in
lung cancer and
esophageal cancer tissues. Furthermore, exogenous ENO1 was overexpressed in cell lines derived from various tissues and single cell proliferation, flowcytometric analysis, and western blotting were performed to determine the cell proliferation rate, cell transformation status, cell cycle progression and the expression of cell cycle regulators, such as
cyclins and
cyclin-dependent kinases, and survival factors, such as MAPK and AKT. The results demonstrated that ENO1 was upregulated in collected panels of
lung cancer tissues, but not in
esophageal cancer tissues. In addition, overexpression of ectopic ENO1 promoted cell proliferation and survival in
lung cancer cell lines, which was not the case in other cells, including an esophageal cell line. Furthermore, mechanistic analyses revealed that ENO1 enhanced cell proliferation by accelerating G1 progression and upregulating G1 phase
cyclin-dependent kinase 6 (CDK6), and improved cell survival by upregulating p38 in the MAPK cascade and increasing p-AKT in the AKT cascade, in particular in
lung cancer cell lines. Overall, the results from the present study demonstrated that ENO1 may contribute to the development of
lung cancers, but not
esophageal cancers.