Abstract
Overexpression of NQO1 is associated with poor prognosis in human cancers including lung, stomach, colon, cervical, and pancreatic cancers. However, the molecular mechanisms underlying the protumorigenic capacities of NQO1 have not been fully elucidated. Here, we investigated this question and determined the molecular mechanisms underlying the roles of NQO1 in glycolysis reprogramming, proliferation, and metastasis breast cancer (BC) cells. The results indicated that NQO1 overexpression in BC cells raises glucose metabolism and metastasis related behaviors. Mechanistically, NQO1 bound to PKLR, activated the AMPK and AKT/mTOR signaling pathway and consequently induced glycolytic reprogramming. In addition, 2-deoxy-d-glucose (2-DG) or 3-bromopyruvate (3-BrPA) influenced proliferation and regulated the expression of genes involved in the epithelial-to-mesenchymal transition (EMT) by restraining glycolytic reprogramming. Finally, overexpression of NQO1 and PKLR in human BC tissues was remarkably related to lymph node (LN) metastasis and poor prognosis. Together, these results demonstrate that the NQO1/PKLR axis can promote the progression of BC by modulating glycolytic reprogramming and suggest that targeting NQO1 and its downstream effectors are promising therapeutic targets for preventing the BC progression.