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Updated: Jan 8, 2026
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Published on: March 15, 2024
Targeting PRDX6-dependent localization and function of GPX4 enhances ferroptosis-mediated tumor suppression
Yameng Hu1, Ziwen Li2, Man Li2
1Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Diseases, State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China; Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Peroxiredoxin 6 (PRDX6) promotes cancer cell resistance to ferroptosis by altering glutathione peroxidase 4 (GPX4) function. Inhibiting PRDX6 enhances ferroptosis, offering a new anticancer therapy strategy.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Inducing ferroptosis is a key anticancer strategy.
- Resistance to ferroptosis limits therapeutic efficacy.
- Understanding resistance mechanisms is crucial for developing effective treatments.
Purpose of the Study:
- To identify key regulators of ferroptosis resistance.
- To elucidate the role of peroxiredoxin 6 (PRDX6) in ferroptosis.
- To explore PRDX6 as a therapeutic target for cancer.
Main Methods:
- Biochemical analyses and structural mutations to study PRDX6-GPX4 interactions.
- Assays to measure lipid peroxidation and ferroptosis.
- In vivo studies using mouse cancer models (liver and ovarian).
- Analysis of clinical data correlating PRDX6 expression with patient survival.
Main Results:
- PRDX6 modulates glutathione peroxidase 4 (GPX4) localization and function, conferring ferroptosis resistance.
- PRDX6's phospholipase A2 activity converts peroxy-phospholipids, and it binds GPX4 via a C47 disulfide bond.
- PRDX6 inhibition combined with ferroptosis inducers suppressed tumor growth in preclinical models.
- High PRDX6 expression is linked to poorer progression-free survival in various human cancers.
Conclusions:
- PRDX6 is a critical mediator of ferroptosis resistance by regulating GPX4.
- Targeting PRDX6 offers a promising strategy to overcome ferroptosis resistance in cancer.
- PRDX6 inhibition enhances ferroptosis, providing a novel therapeutic approach for liver and ovarian cancers.
