Enhanced glycometabolism as a mechanism of NQO1 potentiated growth of NSCLC revealed by metabolomic profiling

NAD(P)H:quinone oxidoreductase 1 (NQO1), a cytoplasmic 2-electron reductase, has been considered as a potential poor prognostic biomarker and a promising therapeutic target for patients with non-small cell lung cancer (NSCLC) due to its frequent overexpression and significantly increased activity in NSCLC. Previous studies have shown that depleting tumor-NQO1 potentiates anoikis and inhibits growth of NSCLC. However, the underlying mechanisms whereby NQO1 potentiates proliferation have not been fully understood. In this study, based on a metabolomics analysis, we found that cell proliferation inhibition upon NQO1 depletion was accompanied by suppressed glycometabolism in NQO1 high expression human NSCLC A549 cells. Also we found that NQO1 depletion significantly decreased the gene expression levels of hexokinase II (HKII), a key mediator of aerobic glycolysis responsible for the transformation of glucose into glucose-6-phosphate. Taken together, we proposed that NQO1 could potentiate NSCLC cell proliferation by enhancing cellular glycometabolism, and HKII is a key mediator of this mechanism.