SRXN1-mediated ferroptosis-disulfidptosis crosstalk network：a new mechanism of tumor radiotherapy
10.3760/cma.j.cn113030-20250321-00106
- VernacularTitle:SRXN1介导的铁死亡-双硫死亡交互网络：肿瘤放疗的新机制
- Author:
Hai WU
1
;
Haiyu LIU
1
;
Yadong WU
1
Author Information
1. 贵州医科大学口腔医学院，贵州医科大学附属口腔医院，贵阳 550001
- Publication Type:Journal Article
- Keywords:
Ferroptosis;
Disulfidptosis;
Sulfiredoxin-1;
Radioresistance;
Oxidative stress
- From:
Chinese Journal of Radiation Oncology
2025;34(12):1264-1268
- CountryChina
- Language:Chinese
-
Abstract:
Radiation therapy is a major treatment modality for many malignant tumors. However, patients exhibit marked individual differences in radiosensitivity. Radiation resistance is persistently strengthened through the antioxidant pathway mediated by sulfiredoxin-1 (SRXN1), forming a key bottleneck in improving therapeutic efficacy. Studies have shown that SRXN1 displays dual regulatory roles in the response to radiation. On one hand, SRXN1 enhances cystine uptake and glutathione synthesis via the Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor erythroid 2-related factor 2 (NRF2)/solute carrier family 7 member 11 (SLC7A11) axis, thereby suppressing lipid peroxidation-induced ferroptosis and promoting radioresistance. On the other hand, excessive activation of the SRXN1-regulated thioredoxin system depletes reduced nicotinamide adenine dinucleotide phosphate, triggering disulfidptosis through actin cytoskeleton depolymerization. This dynamic equilibrium mechanism reveals for the first time that SRXN1 determines radiosensitivity through time-dependent regulation of two interconnected cell death pathways. This article systematically elucidates how SRXN1 dynamically modulates the radiosensitivity of malignant tumors via the ferroptosis-disulfidptosis interaction network, and reviews the underlying molecular mechanisms, providing a theoretical foundation for developing dual-death-inducing nanomedicines.
