RRM2 induces NF-κB-dependent MMP-9 activation and enhances cellular invasiveness

Ribonucleotide reductase is a dimeric enzyme that catalyzes conversion of ribonucleotide 5′-diphosphates to their 2′-deoxynucleotide forms, a rate-limiting step in the production of 2′-deoxyribonucleoside 5′-triphosphates required for DNA synthesis. The ribonucleotide reductase M2 subunit (RRM2) is a determinant of malignant cellular behavior in a range of human cancers. We examined the effect of RRM2 overexpression on pancreatic adenocarcinoma cellular invasiveness and nuclear factor-κB (NF-κB) transcription factor activity. RRM2 overexpression increases pancreatic adenocarcinoma cellular invasiveness and MMP-9 expression in a NF-κB-dependent manner. RNA interference (RNAi)-mediated silencing of RRM2 expression attenuates cellular invasiveness and NF-κB activity. NF-κB is a key mediator of the invasive phenotypic changes induced by RRM2 overexpression.