ArticleJournal of experimental & clinical cancer research : CR2019
Necroptosis regulates tumor repopulation after radiotherapy via RIP1/RIP3/MLKL/JNK/IL8 pathway.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 100 citations in OpenAlex.
- Periostin-CCL3 Feedforward Signaling Loop Promotes Cardiac Fibrosis and Cardiomyocyte Necroptosis in Arrhythmogenic Cardiomyopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Cancer treatment by radioimmunotherapy: insights from a dynamical model of cancer stem cells and hypoxia effects.Scientific reports · 2026Article
- IL-8 positive cancer-associated fibroblasts drive breast cancer progression and immune evasion: insights from GWAS and single-cell transcriptomics.BMC cancer · 2026Article
- MLKL depletion enhances chemotherapy-induced apoptosis in colorectal cancer by prolonged retention of TNFR-I in endosomes.Apoptosis : an international journal on programmed cell death · 2026Article
- PANoptosis-related genes in rheumatoid arthritis synovial tissue: screening, validation, and functional implications.Frontiers in immunology · 2026Article
- Cellular responses to targeted radionuclide therapy: rethinking radiobiology under continuous low dose rates.Frontiers in oncology · 2026Review
- Celastrol ameliorates ulcerative colitis by inhibiting HSP90-mediated necroptosis of intestinal epithelial cells.Frontiers in pharmacology · 2026Article
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- Programmed cell death in triple-negative breast cancer.Cellular & molecular biology letters · 2025Review
- Liquid Plasma Induces Necroptosis Without Inflammatory Responses in Head and Neck Cancer Cells.World journal of oncology · 2025Article
- MiR-21-5p promotes RPE cell necroptosis by targeting Peli1 in a rat model of AMD.In vitro cellular & developmental biology. Animal · 2025Article
- Deciphering the prognostic potential of a necroptosis-related gene signature in head and neck squamous cell carcinoma: a bioinformatic analysis.Translational cancer research · 2025Article
- RIPK1 in necroptosis and recent progress in related pharmaceutics.Frontiers in immunology · 2025Review
- Genomic and transcriptomic profiling of radioresistant prostate and head and neck cancers implicate a BAHD1-dependent modification of DNA damage at the heterochromatin.Cell death & disease · 2024Article
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- Exploring and validating the necroptotic gene regulation and related lncRNA mechanisms in colon adenocarcinoma based on multi-dimensional data.Scientific reports · 2024Article
- Prognostic significance and response to immune checkpoint inhibitors of RIPK3, MLKL and necroptosis in non-small cell lung cancer.Scientific reports · 2024Article
- cGAS-ISG15-RAGE axis reprogram necroptotic microenvironment and promote lymphatic metastasis in head and neck cancer.Experimental hematology & oncology · 2024Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundTumor cell repopulation after radiotherapy is a major cause for the tumor radioresistance and recurrence. This study aims to investigate the underlying mechanism of tumor repopulation after radiotherapy, with focus on whether and how necroptosis takes part in this process.
methodsNecroptosis after irradiation were examined in vitro and in vivo. And the growth-promoting effect of necroptotic cells was investigated by chemical inhibitors or shRNA against necroptosis associated proteins and genes in in vitro and in vivo tumor repopulation models. Downstream relevance factors of necroptosis were identified by western blot and chemiluminescent immunoassays. Finally, the immunohistochemistry staining of identified necroptosis association growth stimulation factor was conducted in human colorectal tumor specimens to verify the relationship with clinical outcome.
resultsRadiation-induced necroptosis depended on activation of RIP1/RIP3/MLKL pathway, and the evidence in vitro and in vivo demonstrated that the inhibition of necroptosis attenuated growth-stimulating effects of irradiated tumor cells on living tumor reporter cells. The JNK/IL-8 were identified as downstream molecules of pMLKL during necroptosis, and inhibition of JNK, IL-8 or IL-8 receptor significantly reduced tumor repopulation after radiotherapy. Moreover, the high expression of IL-8 was associated with poor clinical prognosis in colorectal cancer patients.
conclusionsNecroptosis associated tumor repopulation after radiotherapy depended on activation of RIP1/RIP3/MLKL/JNK/IL-8 pathway. This novel pathway provided new insight into understanding the mechanism of tumor radioresistance and repopulation, and MLKL/JNK/IL-8 could be developed as promising targets for blocking tumor repopulation to enhance the efficacy of colorectal cancer radiotherapy.
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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.