Significant association of PKM2 and NQO1 proteins with poor prognosis in breast cancer

Abstract

Pyruvate kinase M2 (PKM2) and NAD(P)H:quinone oxidoreductase-1 (NQO1) have been known to play significant functions in tumorigenesis and development. The association between PKM2 and NQO1 in breast cancer continues, however, to be unclear. In the present study, according to UALCAN and GEPIA database, the mRNA levels of PKM2 and NQO1 in breast primary tumor were significantly higher compared to normal breast tissue. Consonant with these findings, increased expression of both PKM2 and NQO1 were detected in clinical samples and BC cell lines. More importantly, consolidated high expression of NQO1 and PKM2 were obtained to be related with worse clinical stage, relapse, shorter relapse free survival (RFS), and poorer overall survival (OS) in human breast cancer. We subsequently found that knockdown of NQO1 reduced the protein level of PKM2 significantly. Moreover, deletion of PKM2 significantly reduced colony formation, migration and invasion of BC cells. A positive correlation between PKM2 and NQO1 expression was identified by immunohistochemical analyses of 108 specimens of breast cancer patients (rs = 0.60, P = 0.00). Finally, endogenous Co-IP demonstrated that PKM2 and NQO1 interact in breast cancer cells. The results of this study suggest that the correlation between NQO1 and PKM2 might play a critical role during breast tumourigenesis and serve as novel diagnostic biomarkers for breast cancer.