ArticleNature communications2025
Methionine metabolite spermidine inhibits tumor pyroptosis by enhancing MYO6-mediated endocytosis.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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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.
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Who cites it
5 citing papers in PubMed.
- Gasdermin E: Bridging Pyroptosis, Immunity, and Disease Pathogenesis Toward Precision Intervention.The protein journal · 2026Review
- Myosin VI drives breast cancer progression via SP1/CA9-mediated acidic tumor microenvironment remodeling and subsequent M2 macrophage polarization.Journal for immunotherapy of cancer · 2026Article
- TOLLIP targets GSDME-NT-carrying endocytic vesicles for autophagy to regulate pyroptosis and chemotherapy efficacy.Nature cell biology · 2026Article
- p53 Orchestrates the Immunogenic-Tolerogenic Pyroptosis Switch in Non-Small Cell Lung Cancer: A Systems Biology Approach.Computational and structural biotechnology journal · 2026Article
- Programmed Cell Death in Cancer.MedComm · 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
11 authors.
Funding
Abstract
The connection between amino acid metabolism and pyroptosis remains elusive. Herein, we screen the effect of individual amino acid on pyroptosis and identify that methionine inhibits GSDME-mediated pyroptosis. Mechanistic analyses unveil that MYO6, a unique actin-based motor protein, bridges the GSDME N-terminus (GSDME-NT) and the endocytic adaptor AP2, mediating endolysosomal degradation of GSDME-NT. This degradation is increased by the methionine-derived metabolite spermidine noncanonically by direct binding to MYO6, which enhances MYO6 selectivity for GSDME-NT. Moreover, combination targeted therapies using dietary or pharmacological inhibition in methionine-to-spermidine metabolism in the tumor promotes pyroptosis and anti-tumor immunity, leading to a stronger tumor-suppressive effect in in vivo models. Clinically, higher levels of tumor spermidine and expression of methionine-to-spermidine metabolism-related gene signature predict poorer survival. Conclusively, our research identifies an unrecognized mechanism of pyroptotic resistance mediated by methionine-spermidine metabolic axis, providing a fresh angle for cancer treatment.
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Registered trials
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