Peptide-Based Biosensing of Redox-Active Protein-Heme Complexes Indicates Novel Mechanism for Tumor Survival under...

Signal response of several relevant protein-cofactor interactions, united in one bioassay, may greatly enhance the ability to study the intriguing molecular mechanisms of pathological process such as the tumor immunological process of chronic inflammation and oxidative stress. Here, a peptide-based multiplexed bioassay has been developed and applied in studying the interactions among ferritin, p53, and heme under oxidative stress. In a malignant breast cancer cell line, it can be observed that oxidative stress-triggered nuclear co-translocations of heme and ferritin may lead to direct molecular contact of ferritin with p53, to pass heme to p53, which subsequently sequestered into the cytoplasm, therefore forming a possible new route of tumor survival under oxidative stress, by using the stress to circumvent oxidative stress-induced apoptosis. The observed peroxidase-like activity of ferritin-heme and p53-heme complexes may also contribute to survival. Such activity is observed most prominently in triple negative or the most malignant breast cancer subtype. These results may suggest the possible future use of this bioassay in furthering the understanding of tumor molecular pathology, as well as the early detection, diagnosis, and prognosis of cancer.