ArticleCell research2016
Activation of cell-surface proteases promotes necroptosis, inflammation and cell migration.
Article in Cell research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 104 citations in OpenAlex.
- Soluble tissue factor generated by necroptosis-triggered shedding is responsible for thrombosis.Cell research · 2025Article
- The Multifaceted Role of Calcium Signaling in Regulated Necrosis.Biomolecules · 2025Review
- Pristimerin ameliorates colitis‑induced intestinal mucosal injury by inhibiting intestinal epithelial necroptosis.Molecular medicine reports · 2025Article
- Acute Administration of Edaravone Improves Cognitive Impairment in a Mouse Model of mPFC Ischemia: Crosstalk Between Necroptosis, Neuroinflammation, and Antioxidant Defense.Molecular neurobiology · 2025Article
- The EMCV protein 2B* is required for efficient cell lysis via both caspase-3-dependent and -independent pathways during infection.The Journal of general virology · 2025Article
- Mitochondrial Dysfunction in Congenital Heart Disease.Journal of cardiovascular development and disease · 2025Review
- Establishment and Validation of the Novel Necroptosis-related Genes for Predicting Stemness and Immunity of Hepatocellular CarcinomaCombinatorial chemistry & high throughput screening · 2025Article
- Necroptosis-based glioblastoma prognostic subtypes: implications for TME remodeling and therapy response.Annals of medicine · 2024Article
- DNA encoded peptide library for SARS-CoV-2 3CL protease covalent inhibitor discovery and profiling.RSC chemical biology · 2024Article
- cGAS-ISG15-RAGE axis reprogram necroptotic microenvironment and promote lymphatic metastasis in head and neck cancer.Experimental hematology & oncology · 2024Article
- Necroptosis contributes to non-alcoholic fatty liver disease pathoetiology with promising diagnostic and therapeutic functions.World journal of gastroenterology · 2024Review
- Role of Necroptosis, a Regulated Cell Death, in Seizure and Epilepsy.Neurochemical research · 2024Review
- Article
- A comprehensive analysis of the potential role of necroptosis in hepatocellular carcinoma using single-cell RNA Seq and bulk RNA Seq.Journal of cancer research and clinical oncology · 2023Article
- Virulence Factors ofPathogens (Basel, Switzerland) · 2023Review
- Tumor necroptosis promotes metastasis through modulating the interplay between tumor and host immunity.Oncotarget · 2023Article
- Tumor necroptosis-mediated shedding of cell surface proteins promotes metastasis of breast cancer by suppressing anti-tumor immunity.Breast cancer research : BCR · 2023Article
- Identification and validation of novel signature associated with hepatocellular carcinoma prognosis using Single-cell and WGCNA analysis.International journal of medical sciences · 2023Article
- Non-apoptotic cell death-based cancer therapy: Molecular mechanism, pharmacological modulators, and nanomedicine.Acta pharmaceutica Sinica. B · 2022Review
- Interval-Based Secretomics Unravels Acute-Phase Response in Hepatocyte Model Systems.Molecular & cellular proteomics : MCP · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Necroptosis is a programmed, caspase-independent cell death that is morphologically similar to necrosis. TNF-induced necroptosis is mediated by receptor-interacting protein kinases, RIP1 and RIP3, and the mixed lineage kinase domain-like (MLKL). After being phosphorylated by RIP3, MLKL is translocated to the plasma membrane and mediates necroptosis. However, the execution of necroptosis and its role in inflammation and other cellular responses remain largely elusive. In this study, we report that MLKL-mediated activation of cell-surface proteases of the a disintegrin and metalloprotease (ADAM) family promotes necroptosis, inflammation and cell migration. ADAMs are specifically activated at the early stage of necroptosis when MLKL is phosphorylated and translocated to the cell plasma membrane. Activation of ADAMs induces ectodomain shedding of diverse cell-surface proteins including adhesion molecules, receptors, growth factors and cytokines. Importantly, the shedding of cell-surface proteins disrupts cell adhesion and accelerates necroptosis, while the soluble fragments of the cleaved proteins trigger the inflammatory responses. We also demonstrate that the shedding of E-cadherin ectodomain from necroptotic cells promotes cell migration. Thus, our study provides a novel mechanism of necroptosis-induced inflammation and new insights into the physiological and pathological functions of this unique form of cell death.
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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.