ArticleCell death & disease2021
Proteomic analysis of necroptotic extracellular vesicles.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The trial behind it
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Who cites it
36 citing papers in PubMed, 47 citations in OpenAlex.
- Endothelial Integrin-Linked Kinase (ILK) Deficiency Promotes Endothelial Activation and Cardiovascular Dysfunction via Receptor Interacting Protein Kinase-1 (RIPK1) Enriched-Extracellular Vesicle Signalling.Journal of extracellular vesicles · 2026Article
- Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Engineering the Future: Strategic Advances in Extracellular Vesicle-Mediated Drug Delivery Systems.International journal of nanomedicine · 2026Review
- Clinical relevance of extracellular vesicles in cancer - therapeutic and diagnostic potential.Nature reviews. Clinical oncology · 2025Review
- PARP7 Suppresses Radiation-induced Necroptosis and Abscopal Immunity.Research square · 2025Article
- Extracellular vesicles in cardiovascular homeostasis and disease: potential role in diagnosis and therapy.Nature reviews. Cardiology · 2025Review
- Neuronal Necroptosis Drives Neuroinflammation and Cognitive Decline Independent of Neuronal Cell Death.Aging and disease · 2025Article
- Extracellular Vesicles in the Crosstalk of Autophagy and Apoptosis: A Role for Lipid Rafts.Cells · 2025Review
- Recent Advances of Small Extracellular Vesicles for the Regulation and Function of Cancer-Associated Fibroblasts.International journal of molecular sciences · 2024Review
- Extracellular vesicle-associated DNA: ten years since its discovery in human blood.Cell death & disease · 2024Review
- Yin-Yang: two sides of extracellular vesicles in inflammatory diseases.Journal of nanobiotechnology · 2024Review
- Extracellular Vesicles and Immune System Function: Exploring Novel Approaches to Colorectal Cancer Immunotherapy.Biomedicines · 2024Review
- Micro Trojan horses: Engineering extracellular vesicles crossing biological barriers for drug delivery.Bioengineering & translational medicine · 2024Review
- Exosomes derived from programmed cell death: mechanism and biological significance.Cell communication and signaling : CCS · 2024Review
- Utilizing Extracellular Vesicles for Eliminating 'Unwanted Molecules': Harnessing Nature's Structures in Modern Therapeutic Strategies.Molecules (Basel, Switzerland) · 2024Review
- Transcriptotype-Driven Discovery of Apigenin as a Therapy against Cholestatic Liver Fibrosis: Through Inhibition of PANoptosis and Following Type-I Interferon Responses.Antioxidants (Basel, Switzerland) · 2024Article
- Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches.Journal of extracellular vesicles · 2024Article
- Extracellular vesicle-mediated ferroptosis, pyroptosis, and necroptosis: potential clinical applications in cancer therapy.Cell death discovery · 2024Review
- Protein cargo in extracellular vesicles as the key mediator in the progression of cancer.Cell communication and signaling : CCS · 2024Review
- Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Necroptosis is a regulated and inflammatory form of cell death. We, and others, have previously reported that necroptotic cells release extracellular vesicles (EVs). We have found that necroptotic EVs are loaded with proteins, including the phosphorylated form of the key necroptosis-executing factor, mixed lineage kinase domain-like kinase (MLKL). However, neither the exact protein composition, nor the impact, of necroptotic EVs have been delineated. To characterize their content, EVs from necroptotic and untreated U937 cells were isolated and analyzed by mass spectrometry-based proteomics. A total of 3337 proteins were identified, sharing a high degree of similarity with exosome proteome databases, and clearly distinguishing necroptotic and control EVs. A total of 352 proteins were significantly upregulated in the necroptotic EVs. Among these were MLKL and caspase-8, as validated by immunoblot. Components of the ESCRTIII machinery and inflammatory signaling were also upregulated in the necroptotic EVs, as well as currently unreported components of vesicle formation and transport, and necroptotic signaling pathways. Moreover, we found that necroptotic EVs can be phagocytosed by macrophages to modulate cytokine and chemokine secretion. Finally, we uncovered that necroptotic EVs contain tumor neoantigens, and are enriched with components of antigen processing and presentation. In summary, our study reveals a new layer of regulation during the early stage of necroptosis, mediated by the secretion of specific EVs that influences the microenvironment and may instigate innate and adaptive immune responses. This study sheds light on new potential players in necroptotic signaling and its related EVs, and uncovers the functional tasks accomplished by the cargo of these necroptotic EVs.
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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.