ArticleCell death & disease2017
Dual role of DR5 in death and survival signaling leads to TRAIL resistance in cancer cells.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
34 citing papers in PubMed, 53 citations in OpenAlex.
- Plasma proteomic analysis identified potential therapeutic targets for pulmonary arterial hypertension.iScience · 2026Article
- Helping Apo2L/TRAIL in the Battle: Synergistic Therapeutic Approaches for Cancer Therapies.International journal of molecular sciences · 2026Review
- b-AP15 enhances TRAIL-induced cell death in HNSCC via the induction of ROS/JNK/DR5 signalling.Cancer gene therapy · 2026Article
- DR5 CAR-T cells target melanoma and suppress MDSCs with minimal toxicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Applying Ultrasound to Mechanically and Noninvasively Sensitize Prostate Tumors to TRAIL-Mediated Apoptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Combination of multivalent DR5 receptor clustering agonists and histone deacetylase inhibitors for treatment of colon cancer.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Review
- Methodological Approaches to Experimental Evaluation of Neuroprotective Action of Potential Drugs.International journal of molecular sciences · 2024Review
- Review
- TRAIL-dependent apoptosis of peritoneal mesothelial cells by NK cells promotes ovarian cancer invasion.iScience · 2023Article
- Oxaliplatin Enhances the Apoptotic Effect of Mesenchymal Stem Cells, Delivering Soluble TRAIL in Chemoresistant Colorectal Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Pyrazolo[4,3-International journal of molecular sciences · 2023Article
- BdLT-Seq as a barcode decay-based method to unravel lineage-linked transcriptome plasticity.Nature communications · 2023Article
- Macrophage-like THP-1 Cells Derived from High-Density Cell Culture Are Resistant to TRAIL-Induced Cell Death via Down-Regulation of Death-Receptors DR4 and DR5.Biomolecules · 2022Article
- 3-Dimensional Model to Study Apoptosis Induction of Activated Natural Killer Cells Conditioned Medium Using Patient-Derived Colorectal Cancer Organoids.Frontiers in cell and developmental biology · 2022Article
- Bioymifi, a novel mimetic of TNF-related apoptosis-induced ligand (TRAIL), stimulates eryptosis.Medical oncology (Northwood, London, England) · 2021Article
- Impact of Type I Interferons on Susceptibility to Bacterial Pathogens.Trends in microbiology · 2021Review
- Combination of oridonin and TRAIL induces apoptosis in uveal melanoma cells by upregulating DR5.International journal of ophthalmology · 2021Article
- CUDC-907 enhances TRAIL-induced apoptosis through upregulation of DR5 in breast cancer cells.Journal of cell communication and signaling · 2020Article
- Genetically Modified DR5-Specific TRAIL Variant DR5-B Revealed Dual Antitumor and Protumoral Effect in Colon Cancer Xenografts and an Improved Pharmacokinetic Profile.Translational oncology · 2020Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Besides its tumor-selective apoptotic activity, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) promotes pro-survival, proliferative or migratory signaling (NF-κB, PI3K/Akt, MAPK and JNK; referred to as 'non-apoptotic' cascades). Indeed, apoptosis and non-apoptotic signaling can be activated in clonal populations of cancer cells in response to treatment and, as a result, only a part of the initial cellular population dies while a fraction survives and develops resistance to TRAIL-induced apoptosis (referred to as 'fractional survival'). Notably, the molecular characterization of the protein platforms streaming into tumoricidal versus tumor-promoting cascades that control fractional survival remained elusive. Here we demonstrate that, in the context of DR4-DR5-DcR2 hetero-oligomeric complexes, a single death receptor (DR5) suffices to assemble composite plasma membrane-proximal pro-apoptotic/pro-survival platforms that propagate TRAIL signaling to both death and survival pathways in clonal populations of cancer cells. Moreover, we show that while all members of TRAIL-induced complexes support survival, none of them acted exclusively pro-apoptotic. Indeed, key apoptotic proteins as FADD and procaspase-8 were also involved in transducing non-apoptotic signaling in response to this cytokine. Collectively, this study reveals the Janus faces of DR5, and the contributions of other death complex components in fractional survival that foster the generation of resistance. Our data highlight a new level of complexity in TRAIL signaling and point to an improved therapeutic rationale in view of hitherto disappointing results.
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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.