ArticleCell death and differentiation2025
GPX4-AUTAC induces ferroptosis in breast cancer by promoting the selective autophagic degradation of GPX4 mediated by TRAF6-p62.
Article in Cell death and differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed.
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- Strategies for Targeting Mitochondria in the Treatment of Breast Cancer.ACS pharmacology & translational science · 2026Review
- A Biomimetic Nanoparticle System Intercepts and Degrades Thrombospondin-1 to Restore Vascular Homeostasis After Ischemic Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanotransduction Failure and Molecular Rescue in Gastric Cancer: Kinetotherapy Across the IL-6/STAT3-Myostatin/ACVR2B-Akt/mTOR Axis.Medical sciences (Basel, Switzerland) · 2026Review
- Zinc-binding protein metallothionein 3 protects vascular smooth muscle cells from ferroptosis via blocking lysosomal degradation of GPX4.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Cephaeline promotes ferroptosis in breast cancer via p53/SLC7A11/GPX4 axis.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Article
- Molecular engineering of lysosome-based degraders unveils a rapidly expanding therapeutic strategy.Autophagy · 2026Review
- USP20 governs tyrosine kinase inhibitors resistance through ferroptosis evasion by targeting GPX4 in cancers.Redox biology · 2026Article
- Review
- Decoding the spatiotemporal characteristics of ferroptosis: reshaping tumour therapeutic strategies.Experimental hematology & oncology · 2026Review
- Targeted Degradation of eEF2K by a Structure-Guided PROTAC Strategy for the Treatment of Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Role of Se-Containing Glutathione Peroxidases and Thioredoxin Reductases in Oncogenesis: Expression Paradoxes and Therapeutic Prospects.Antioxidants (Basel, Switzerland) · 2026Review
- Hsa_circ_0001756, a novel biomarker, promotes breast cancer progression via miR-584-5p/TRAF6 signaling axis.Translational cancer research · 2026Article
- Targeting glutathione peroxidase 4 in ferroptosis: from immune regulation to pharmacological development and translational applications.Frontiers in pharmacology · 2026Review
- Ferroptosis in biliary tract cancer: Molecular mechanisms and therapeutic applications (Review).International journal of oncology · 2026Review
- Protein Post-Translational Modifications in the Regulation of Ferroptosis: New Opportunities and Challenges for Cancer Immunotherapy.International journal of biological sciences · 2026Review
- Targeted protein degradation: species, diseases and efficient utilization.Journal of translational medicine · 2025Review
- Serine/Threonine Kinase 33 as a Novel Target of Bufalin in Treatment of Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Crosstalk Between Allergic Inflammation and Autophagy.International journal of molecular sciences · 2025Review
- Natural Compounds as Modulators of Ferroptosis: Mechanistic Insights and Therapeutic Prospects in Breast Cancer.Biomolecules · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
Emerging evidence indicates that activation of ferroptosis by inhibition of glutathione peroxidase 4 (GPX4) may be exploited as a therapeutic strategy to suppress tumor growth and progression. However, application of GPX4 inhibitors in cancer treatment is hampered by their poor selectivity, which results in unfavorable toxicity. Herein, we identified GPX4 as a candidate for the autophagy pathway. We showed that GPX4 is ubiquitinated by TNF receptor-associated factor 6 (TRAF6), which promotes its recognition by p62 and leads to its selective autophagic degradation. Utilizing targeted protein degradation (TPD) approach, we developed a GPX4-targeted AUTAC and demonstrated that GPX4-AUTAC promoted the ubiquitination of GPX4, and enhanced the binding with GPX4 and p62, leading to the selective autophagy-dependent degradation of GPX4. Furthermore, GPX4-AUTAC treatment strongly induced ferroptosis and exhibited potent anti-cancer activity against breast cancer in vitro, in vivo, and patient-derived organoids (PDOs). Combination treatment of GPX4-AUTAC with sulfasalazine, a ferroptotic inducer, or chemotherapy drugs showed a synergistic anti-cancer effect against breast cancer. These results uncover a new targeted degradation strategy for GPX4 by inducing selective autophagy and provide a rationale for the use of GPX4-AUTAC as a novel therapeutic approach to treatment of breast cancer.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.