ArticleNature communications2024
Necroptosis enhances 'don't eat me' signal and induces macrophage extracellular traps to promote pancreatic cancer liver metastasis.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Necroptosis in pancreatic cancer: Molecular mechanisms and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026Pooled it
- Necroptosis and the RIPK1-RIPK3-MLKL pathway in chronic kidney disease: mechanisms, crosstalk, and therapeutic opportunities.Renal failure · 2026Review
- Digoxin Alleviates Osteoarthritis by Inhibiting Macrophage Extracellular Trap Formation via Disruption of the LSP1-SOD1 Interaction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- 25 Years of Cancer Immunoediting: Dendritic Cells and Macrophages Filled the Missing Gap.Cancers · 2026Review
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Review
- Macrophage Extracellular Traps in Immunity and Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Article
- HIF-1α Promotes Macrophage Extracellular Trap Formation and Exacerbates Acute Lung Injury in Neonatal Sepsis.Biomedicines · 2026Article
- Programmed cell death in cancer: targeting necroptosis to kill tumor cell.Cell death discovery · 2026Review
- Galectin-9Aging cell · 2026Article
- The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- Dying cells as architects of the stem cell niche: a conserved mechanism driving tissue regeneration and tumor therapy resistance.Cell communication and signaling : CCS · 2026Review
- Metabolic syndrome necroptosis: disease implications and therapeutic targeting.Journal of physiology and biochemistry · 2026Review
- Programmed cell death inhibitors: a new hope for cancer therapy?World journal of surgical oncology · 2026Review
- The Role of Low CD36 Expression in the Development of Non-Small Cell Lung Cancer and Its Potential for Therapy.Cancers · 2026Review
- Remodeling the tumor immune microenvironment: mechanisms of crosstalk between regulated cell death macrophages.Frontiers in immunology · 2026Review
- Rac/Cdc42 inhibitors target pancreatic cancer cells and macrophages in the tumor microenvironment.Cancer treatment and research communications · 2026Article
- Single-Cell Sequencing Unravels Pancreatic Cancer: Novel Technologies Reveal Novel Aspects of Cellular Heterogeneity and Inform Therapeutic Strategies.Biomedicines · 2025Review
- GADD45β inhibits RIPK3-mediated NF-κB activation by interfering with NEMO-RIPK1-RIPK3 interactions.Cell death discovery · 2025Article
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Authors and funding
18 authors.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 'don't eat me' signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial-mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.
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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 Socratic graph.