In colorectal cancer, redox signaling exhibits two Janus faces: On the one hand, NOX1 up-regulation and derived hydrogen peroxide enhance Wnt/β-catenin and Notch proliferating pathways; on the other hand, ROS may disrupt tumor progression through different pro-apoptotic mechanisms.
Gene-neighbour and gene set enrichment analyses revealed that NOX1/2/5 were strongly correlated with genes associated with cancer cell survival and metastasis, whereas increased NOX4 and DUOX1 expression was associated with genes that inhibit tumour progression.
Here, to further investigate the role of HIPK2 in p53 activation, we started with the finding that HIPK2 inhibition upregulated Nox1, a homolog of the catalytic subunit of the superoxide-generating NADPH oxidase, involved in tumor progression and ROS production.