Conclusion
Mammalian target of rapamycin pathway promotes aerobic glycolysis in esophageal squamous cell carcinoma by upregulating pyruvate kinase M2 isoform. Both proteins can serve as molecular targets for novel therapeutic strategies.
Methods
Immunohistochemical staining was used to compare pyruvate kinase M2 isoform and phospho-mammalian target of rapamycin expression in 30 human pathological esophageal squamous cell carcinoma sections and 30 nontumoral esophageal tissues. Short hairpin RNA was used to inhibit pyruvate kinase M2 isoform and activate mammalian target of rapamycin, after which we monitored changes in glucose consumption and lactate production. Finally, we determined the expression of pyruvate kinase M2 isoform and the mammalian target of rapamycin downstream transcription factor hypoxia-inducible factor-1α, as well as glucose consumption and lactate production, following the modification of mammalian target of rapamycin expression.
Results
Immunohistochemical staining showed that both phospho-mammalian target of rapamycin and pyruvate kinase M2 isoform expression were higher in esophageal squamous cell carcinoma than in nontumor tissues. Glucose consumption and lactate production measurements demonstrated that altering mammalian target of rapamycin and pyruvate kinase M2 isoform levels caused corresponding changes in glycolysis in esophageal squamous cell carcinoma cells. When mammalian target of rapamycin was activated or inhibited, expression of pyruvate kinase M2 isoform and hypoxia-inducible factor-1α as well as glycolysis were altered, indicating that mammalian target of rapamycin regulates pyruvate kinase M2 isoform via the downstream transcription factor hypoxia-inducible factor-1α, thereby affecting glycolysis in esophageal squamous cell carcinoma.