ArticleCell death and differentiation2020
Stress-induced TRAILR2 expression overcomes TRAIL resistance in cancer cell spheroids.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Podoplanin immunoexpression in odontogenic lesions: a systematic review, meta-analysis, and integrated bioinformatic analysis.Diagnostic pathology · 2024Pooled it
- REDD1/DDIT4 counteracts endoplasmic reticulum stress-induced apoptosis by controlling the expression of death receptor TRAILR2/DR5 in cancer cells.Cell death & disease · 2026Article
- Interplay of ferroptotic and apoptotic cell death and its modulation by BH3-mimetics.Cell death and differentiation · 2025Article
- Basic and applied research progress of TRAIL in hematologic malignancies.Blood science (Baltimore, Md.) · 2025Review
- Ionizing Radiation Increases Death Receptor 5 (DR5)-Mediated Cell Death, but Not Death Receptor 4 (DR4)-Mediated Cell Death in 3D Tumor Spheroids.International journal of molecular sciences · 2025Article
- IRE1 RNase controls CD95-mediated cell death.EMBO reports · 2024Article
- Targeting Death Receptor 5 (DR5) for the imaging and treatment of primary bone and soft tissue tumors: an update of the literature.Frontiers in molecular biosciences · 2024Review
- Stressed target cancer cells drive nongenetic reprogramming of CAR T cells and solid tumor microenvironment.Nature communications · 2023Article
- Stressed target cancer cells drive nongenetic reprogramming of CAR T cells and tumor microenvironment, overcoming multiple obstacles of CAR T therapy for solid tumors.Research square · 2023Article
- Nanomedicine strategies to counteract cancer stemness and chemoresistance.Exploration of targeted anti-tumor therapy · 2023Review
- Three-dimensional in vitro culture models in oncology research.Cell & bioscience · 2022Review
- Glioblastoma, from disease understanding towards optimal cell-based in vitro models.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Induction of DR5-Dependent Apoptosis by PGAMolecules (Basel, Switzerland) · 2022Article
- No Time to Die: How Kidney Cancer Evades Cell Death.International journal of molecular sciences · 2022Review
- cFLIP downregulation is an early event required for endoplasmic reticulum stress-induced apoptosis in tumor cells.Cell death & disease · 2022Article
- Macro- and micro-nutrient-based multiplex stress conditions modulate in vitro tumorigenesis and aggressive behavior of breast cancer spheroids.In vitro models · 2022Article
- Bixin Prevents Colorectal Cancer Development through AMPK-Activated Endoplasmic Reticulum Stress.BioMed research international · 2022Article
- Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies.International journal of molecular sciences · 2021Review
- Behind the Adaptive and Resistance Mechanisms of Cancer Stem Cells to TRAIL.Pharmaceutics · 2021Review
- Marizomib sensitizes primary glioma cells to apoptosis induced by a latest-generation TRAIL receptor agonist.Cell death & disease · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The influence of 3D microenvironments on apoptosis susceptibility remains poorly understood. Here, we studied the susceptibility of cancer cell spheroids, grown to the size of micrometastases, to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Interestingly, pronounced, spatially coordinated response heterogeneities manifest within spheroidal microenvironments: In spheroids grown from genetically identical cells, TRAIL-resistant subpopulations enclose, and protect TRAIL-hypersensitive cells, thereby increasing overall treatment resistance. TRAIL-resistant layers form at the interface of proliferating and quiescent cells and lack both TRAILR1 and TRAILR2 protein expression. In contrast, oxygen, and nutrient deprivation promote high amounts of TRAILR2 expression in TRAIL-hypersensitive cells in inner spheroid layers. COX-II inhibitor celecoxib further enhanced TRAILR2 expression in spheroids, likely resulting from increased ER stress, and thereby re-sensitized TRAIL-resistant cell layers to treatment. Our analyses explain how TRAIL response heterogeneities manifest within well-defined multicellular environments, and how spatial barriers of TRAIL resistance can be minimized and eliminated.
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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.