ArticleCell death & disease2015
Differential roles of RIPK1 and RIPK3 in TNF-induced necroptosis and chemotherapeutic agent-induced cell death.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 1 of them a synthesis that pooled it.
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Who cites it
141 citing papers in PubMed, 1 synthesis or guideline pooled it, 247 citations in OpenAlex.
- Prognostic and clinicopathological significance of MLKL expression in cancer patients: a meta-analysis.BMC cancer · 2018Pooled it
- Igniting antitumour immunity with cancer cell pyroptosis.Nature reviews. Cancer · 2026Review
- Bioorthogonal catalytic centres engineered for gastrointestinal stabilization provide oral delivery for the treatment of gastric cancer.Journal of nanobiotechnology · 2026Article
- Reactivating necroptosis in colorectal cancer potentiates chemotherapy and antitumor immune responses.Cancer letters · 2026Article
- MMP14-Dependent Activation of TGF-β Signaling Enhances Malignancies via Promoting Necroptosis in Glioblastoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Trigger Points of Necroptosis (RIPK1, RIPK3, and MLKL)-Promising Horizon or Blind Alley in Therapy of Colorectal Cancer?International journal of molecular sciences · 2025Review
- Mechanism and role of regulated cell death in tumor immunity and immunotherapy.Cancer communications (London, England) · 2025Review
- Depletion of oxysterol-binding proteins by OSW-1 triggers RIP1/RIP3-independent necroptosis and sensitization to cancer immunotherapy.Cell death and differentiation · 2025Article
- Spliceosome inhibition induces Z-RNA and ZBP1-driven cell death in small cell lung cancer.Cell reports · 2025Article
- Syncytial death mediated by oncolytic rVSV-NDV dynamically activates immunogenic apoptosis and necroptosis in human lung cancer cells.Molecular therapy. Oncology · 2025Article
- Decoding the immune landscape in Ewing sarcoma pathogenesis: The role of tumor infiltrating immune cells and immune milieu.Journal of bone oncology · 2025Review
- Epigenetic Inactivation of RIPK3-Dependent Necroptosis Augments Cisplatin Chemoresistance in Human Osteosarcoma.International journal of molecular sciences · 2025Article
- Neuronal Injury after Ischemic Stroke: Mechanisms of Crosstalk Involving Necroptosis.Journal of molecular neuroscience : MN · 2025Review
- Necroptosis of hippocampal neurons in paclitaxel chemotherapy-induced cognitive impairment mediates microglial activation via TLR4/MyD88 signaling pathway.Open medicine (Warsaw, Poland) · 2025Article
- Necroptosis-based glioblastoma prognostic subtypes: implications for TME remodeling and therapy response.Annals of medicine · 2024Article
- SPOP-mediated RIPK3 destabilization desensitizes LPS/sMAC/zVAD-induced necroptotic cell death.Cellular and molecular life sciences : CMLS · 2024Article
- Exploring and validating the necroptotic gene regulation and related lncRNA mechanisms in colon adenocarcinoma based on multi-dimensional data.Scientific reports · 2024Article
- Necroptosis stimulates interferon-mediated protective anti-tumor immunity.Cell death & disease · 2024Article
- Necroptosis induced by ruthenium (II) complexes as mitochondrial disruptors.Cell death discovery · 2024Article
- Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024Review
81 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Apoptosis is a key mechanism for metazoans to eliminate unwanted cells. Resistance to apoptosis is a hallmark of many cancer cells and a major roadblock to traditional chemotherapy. Recent evidence indicates that inhibition of caspase-dependent apoptosis sensitizes many cancer cells to a form of non-apoptotic cell death termed necroptosis. This has led to widespread interest in exploring necroptosis as an alternative strategy for anti-cancer therapy. Here we show that in human colon cancer tissues, the expression of the essential necroptosis adaptors receptor interacting protein kinase (RIPK)1 and RIPK3 is significantly decreased compared with adjacent normal colon tissues. The expression of RIPK1 and RIPK3 was suppressed by hypoxia, but not by epigenetic DNA modification. To explore the role of necroptosis in chemotherapy-induced cell death, we used inhibitors of RIPK1 or RIPK3 kinase activity, and modulated their expression in colon cancer cell lines using short hairpin RNAs. We found that RIPK1 and RIPK3 were largely dispensable for classical chemotherapy-induced cell death. Caspase inhibitor and/or second mitochondria-derived activator of caspase mimetic, which sensitize cells to RIPK1- and RIPK3-dependent necroptosis downstream of tumor necrosis factor receptor-like death receptors, also did not alter the response of cancer cells to chemotherapeutic agents. In contrast to the RIPKs, we found that cathepsins are partially responsible for doxorubicin or etoposide-induced cell death. Taken together, these results indicate that traditional chemotherapeutic agents are not efficient inducers of necroptosis and that more potent pathway-specific drugs are required to fully harness the power of necroptosis in anti-cancer therapy.
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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.