ArticleRedox biology2025
Inhibition of glutathione peroxidase 4 suppresses gastric cancer peritoneal metastasis via regulation of RCC2 homeostasis.
Article in Redox biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Ferroptosis regulatory networks as therapeutic sensitizers in combination therapy for hepatocellular carcinoma (Review).Oncology letters · 2026Review
- Selenoproteins: Minute yet vital players governing cellular fate.Genes & diseases · 2026Review
- Proteomic profiling identifies an oncogene ITGA2 and its downstream targets in gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- DLEU2 promotes the migration and invasion of papillary thyroid carcinoma cells through the ELAVL1/RCC2 axis.Functional & integrative genomics · 2026Article
- Refined immune-based molecular subtypes of gastric cancer: Integrating mismatch repair status and tumor microenvironment for enhanced immunotherapy prediction.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2026Article
- Phosphorylated-EGFR and MMP7 upregulation in gastric cancer: Association with metastasis and poor prognosis.Oncology letters · 2026Article
- Solasonine inhibits NSCLC malignant progression by regulating SLC7A11 ubiquitination degradation and inducing ferroptosis.Respiratory research · 2026Article
- Ferroptosis and metastasis: molecular checkpoints, microenvironmental dynamics, and therapeutic opportunities.Molecular cancer · 2026Review
- Inhibition of integrin α3 suppresses gastric cancer progression via STAT3-mediated regulation of SLC1A5-dependent glutamine uptake.Journal of gastroenterology · 2025Article
- RCC2 and CD24 cooperate to modulate prostate cancer progression through vimentin ubiquitination and β-catenin activation.The Journal of clinical investigation · 2025Article
- GPX4 knockdown suppresses M2 macrophage polarization in gastric cancer by modulating kynurenine metabolism.Theranostics · 2025Article
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16 authors.
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Abstract
Gastric cancer (GC) is one of the most lethal malignancies due to high metastatic rate, making the identification of new therapeutic targets critical for developing effective anti-GC treatments. Glutathione peroxidase 4 (GPx4), a key regulator of ferroptosis and redox homeostasis, contributes to progression and influences patient survival. However, the molecular mechanism by which GPx4 drives GC progression has not been fully illuminated. In this study, we found that GPx4 was overexpressed and negatively associated with poor prognosis and distant metastasis, as confirmed by single-cell RNA sequencing (scRNA-seq) and validation with retrospective clinical samples. GPx4 knockdown suppressed GC invasion, migration and peritoneal metastasis in vitro and in vivo. Proteomic analysis revealed that GPx4 expression regulated the Homeostasis of RCC2, an oncogene link to epithelial-mesenchymal transition (EMT). Furthermore, we demonstrated that the reactive oxygen species (ROS) accumulation induced by GPx4 inhibition or knockdown activated aurora A phosphorylation, leading to RCC2 ubiquitination and degradation, thereby suppressing peritoneal metastasis in GC. We also identified that the Thr418 phosphorylation site is crucial for RCC2 ubiquitination at the K377, initiating its degradation in response to ROS. In conclusion, our results indicate that GPx4 acts as an oncogene in GC, and that suppressing GPx4 prevents GC progression and metastasis by promoting ROS-induced RCC2 ubiquitination and degradation.
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