ArticleJournal of experimental & clinical cancer research : CR2023
ERRα promotes glycolytic metabolism and targets the NLRP3/caspase-1/GSDMD pathway to regulate pyroptosis in endometrial cancer.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 67 citations in OpenAlex.
- Novel inhibitors against Cryptosporidium parvum through blocking its energy metabolism.PLoS neglected tropical diseases · 2026Article
- CCT2 defines a highly cisplatin-resistant and poor-prognosis subtype of lung adenocarcinoma.Oncology letters · 2026Article
- The NLRP3 inflammasome as a dynamic context-dependent regulator: mechanisms, disease progression, and therapeutic implications.Journal of translational medicine · 2026Review
- Metabolic activation of LDHA by ERRα represses inflammasome-dependent pyroptosis and promotes ovarian cancer chemoresistance.Cell death & disease · 2026Article
- Estrogen receptor β deficiency increases susceptibility to sepsis through metabolic reprogramming-induced macrophage pyroptosis.The Journal of clinical investigation · 2026Article
- Long non-coding RNA STMN1P2 promotes breast cancer doxorubicin resistance by inhibiting pyroptosis through the hnRNPU-EZH2-TARF6-MALT1-caspase-1 pathway.Acta pharmacologica Sinica · 2026Article
- Organelle stress in NLRP3 inflammasome: a central mediator of neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Glycolytic reprogramming in cancer: immune crosstalk, nutrient competition, and supportive care perspectives.Frontiers in immunology · 2026Review
- Mitochondrial LINC01133 regulates pyroptosis and calcium homeostasis in cisplatin-resistant lung adenocarcinoma.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- The NLRP3 inflammasome in gynecological cancers: a double-edged sword shaping the immune microenvironment and immunotherapy response.Frontiers in immunology · 2026Review
- Age and sex: dual drivers remodeling the anti-tumor immune microenvironment and shaping personalized immuno-oncology.Frontiers in immunology · 2026Review
- Inflammasomes and pyroptosis in cancer: mechanisms and therapeutic advances.Journal of hematology & oncology · 2025Review
- Melatonin Modulates Glucose Metabolism Reprogramming via Targeting G6PD to Alleviate Lead-Induced Hepatocytes Pyroptosis in Common Carp (Cyprinus carpio L.).Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review: Progress of the NLRP3 inflammasome in tumours and perspectives for cholangiocarcinoma.Cell communication and signaling : CCS · 2025Review
- PANoptosis in cancer: molecular mechanisms and therapeutic potential.Cancer gene therapy · 2025Review
- Precision delivery of estrogen receptor antagonists using bioorthogonal chemistry-based intelligent nanocarriers to overcome cervical cancer drug resistance.Materials today. Bio · 2025Review
- Antagonism of estrogen-related receptor-α inhibits mitochondrial oxidative phosphorylation and reduces M2 macrophage infiltration in endometrial cancer.Journal for immunotherapy of cancer · 2025Article
- Identification of clusters related to programmed cell death and potential prognostic biomarkers for immunotherapy response in endometrial cancer.Scientific reports · 2025Article
- Targeting pyroptosis for cancer immunotherapy: mechanistic insights and clinical perspectives.Molecular cancer · 2025Review
- The Role of Cancer Organoids in Ferroptosis, Pyroptosis, and Necroptosis: Functions and Clinical Implications.Biomolecules · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundTumor cells can resist chemotherapy-induced pyroptosis through glycolytic reprogramming. Estrogen-related receptor alpha (ERRα) is a central regulator of cellular energy metabolism associated with poor cancer prognosis. Herein, we refine the oncogenic role of ERRα in the pyroptosis pathway and glycolytic metabolism.
methodsThe interaction between ERRα and HIF-1α was verified using co-immunoprecipitation. The transcriptional binding sites of ERRα and NLRP3 were confirmed using dual-luciferase reporter assay and cleavage under targets and tagmentation (CUT&Tag). Flow cytometry, transmission electron microscopy, scanning electron microscopy, cell mito stress test, and extracellular acidification rate analysis were performed to investigate the effects of ERRα on the pyroptosis pathway and glycolytic metabolism. The results of these experiments were further confirmed in endometrial cancer (EC)-derived organoids and nude mice. In addition, the expression of ERRα-related pyroptosis genes was analyzed using The Cancer Genome Atlas and Gene Expression Omnibus database.
resultsTriggered by a hypoxic microenvironment, highly expressed ERRα could bind to the promoter of NLRP3 and inhibit caspase-1/GSDMD signaling, which reduced inflammasome activation and increased pyroptosis resistance, thereby resulting in the resistance of cancer cells to cisplatin. Moreover, ERRα activated glycolytic rate-limiting enzyme to bridge glycolytic metabolism and pyroptosis in EC. This phenomenon was further confirmed in EC-derived organoids and nude mice. CUT & Tag sequencing and The Cancer Genome Atlas database analysis showed that ERRα participated in glycolysis and programmed cell death, which resulted in EC progression.
conclusionsERRα inhibits pyroptosis in an NLRP3-dependent manner and induces glycolytic metabolism, resulting in cisplatin resistance in EC cells.
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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.