Redox guardian or oncogenic driver? The dual roles of PRDX1 in tumorigenesis

Peroxiredoxin 1 (PRDX1) is a thiol-dependent peroxidase with paradoxical roles in cancer. In response to oxidative stress and hyperoxidation of its peroxidatic cysteine, PRDX1 undergoes reversible oligomerization, switching from a peroxidase to a molecular chaperone, thereby dictating context-dependent tumor effects. In early malignancy, PRDX1 suppresses transformation by limiting oxidative DNA damage and inhibiting oncogenic signaling (c-Myc, PTEN/AKT). However, PRDX1 overexpression in advanced cancers promotes survival, proliferation, and chemoresistance via MAPK modulation, DNA repair enhancement, and tumor microenvironment remodeling via TLR4-mediated immune modulation. Elevated PRDX1 correlates with poor prognosis in lung, breast, liver, bladder, and colorectal cancers. Pharmacological targeting with covalent inhibitors (celastrol derivatives, adenanthin, natamycin) induces oxidative stress and apoptosis in preclinical models, yet isoform selectivity and patient stratification remain unresolved. This review synthesizes PRDX1's dual tumor-suppressive and oncogenic functions, highlighting mechanisms underlying its redox-switching behavior and exploring its potential as a diagnostic biomarker and therapeutic target. Understanding PRDX1's structural dynamics and protein interactions will enable rational design of context-appropriate interventions in precision oncology.