PRX5 as a Redox Regulator of STAT3 Signaling in Cancer Stem Cells

Peroxiredoxin 5 (PRX5) is an atypical 2-Cys peroxiredoxin distributed across mitochondria, peroxisomes, cytosol, and nucleus. Unlike other PRX isoforms, PRX5 acts not only as a reactive oxygen species (ROS) scavenger but also as a redox-dependent regulator of oncogenic signaling. Cancer stem cells (CSCs) maintain low intracellular ROS to preserve self-renewal and drug resistance, and PRX5 has emerged as a key mediator of this redox control. This review examines the. PRX5-ROS-Signal Transducer and Activator of Transcription 3 (STAT3) axis in CSC biology. We present mechanistic evidence demonstrating that PRX5-mediated redox balance protects STAT3 from oxidative inactivation and proteasomal degradation, sustaining its transcriptional activity and the stable expression of Octamer-binding transcription factor4 (OCT4), SRY-box transcription factor 2 (SOX2), and NANOG, with particular relevance to colorectal cancer. We further discuss how this axis integrates with oncogenic networks and represents a targetable vulnerability. Collectively, the evidence supports PRX5 as a prognostic biomarker and therapeutic target for disrupting CSC maintenance.