Glycolytic phenotype of non-small cell lung cancer: Implication of anaerobic glycolysis on malignant potential

Abstract

9634 Background: One of the most common phenotypes of malignancy is their ability to metabolize glucose at high rates. Recently, a mitochondria bound type II hexokinase (HK2) is focused on in the high glycolytic phenotype. On the other hand, the expression of the β-H+-ATP-synthase (β-F1-ATPase), which is required for aerobic energy-provision, is reported to down-reulated in colon and kidney cancer. To invstigate the status and significance of glucose catabolism in non-small cell cancer (NSCLC), expression of glycolytic enzymes were examined. Methods: HK2, glycolytic glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and β-H+-ATP-synthase (β-F1-ATPase) mRNA were quantified by a real-time reverse transcription polymerase chain reaction in both tumor and non-tumor-bearing lung tissues of 40 patients with NSCLC. To analyze the role of HK2 in vitro, a NSCLC cell line (PC9) was transfected with small interfering RNA, and examined for its growth. Results: All three mRNAs of enzymes were higher expressed in tumor tissues than in normal tissues. The high expression level of anaerobic enzymes such as HK2 and GAPDH showed positive relationship with poor prognosis, whereas that of β-F1-ATPase showed no relationship with prognosis.Moreover, the high expression of these two glycolytic molecules also had positive relationship with smoking and pathological staging. Introduction of HK2 siRNA into PC9 leads to significanct growth inhibition in MTS assay. Conclusion: Glycolytic enzymes involved in energy provision in anaerobic condition are related to tumor progression, and HK2 can be a crucial target for arresting or slowing the growth of NSCLC. No significant financial relationships to disclose.