ArticleMolecular biology of the cell2013
Cells surviving fractional killing by TRAIL exhibit transient but sustainable resistance and inflammatory phenotypes.
Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed.
- Regulated cell death plasticity in cancer: thresholds, reversibility, and therapeutic failure.Journal of translational medicine · 2026Review
- Transition between cell states of sensitivity reveals molecular vulnerability of drug-tolerant cells.Molecular systems biology · 2025Article
- Unlocking mitochondrial dysfunction-associated senescence (MiDAS) with NADTranslational oncology · 2024Article
- Stress in the metastatic journey - the role of cell communication and clustering in breast cancer progression and treatment resistance.Disease models & mechanisms · 2024Article
- Cell cycle plasticity underlies fractional resistance to palbociclib in ER+/HER2- breast tumor cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The ability to sense the environment is heterogeneously distributed in cell populations.eLife · 2024Article
- Non-lethal outcomes of engaging regulated cell death pathways in cancer.Nature cancer · 2023Review
- BdLT-Seq as a barcode decay-based method to unravel lineage-linked transcriptome plasticity.Nature communications · 2023Article
- The role of the immune response and inflammatory pathways in TNF-related apoptosis-inducing ligand (TRAIL) resistance in triple-negative breast cancer cells.American journal of cancer research · 2023Article
- Mathematical modeling of regulatory networks of intracellular processes - Aims and selected methods.Computational and structural biotechnology journal · 2023Review
- Modeling Cellular Signaling Variability Based on Single-Cell Data: The TGFβ-SMAD Signaling Pathway.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Relating individual cell division events to single-cell ERK and Akt activity time courses.Scientific reports · 2022Article
- Application of Sensitivity Analysis to Discover Potential Molecular Drug Targets.International journal of molecular sciences · 2022Article
- Quantification of long-term doxorubicin response dynamics in breast cancer cell lines to direct treatment schedules.PLoS computational biology · 2022Article
- TRAIL signaling promotes entosis in colorectal cancer.The Journal of cell biology · 2021Article
- Mutagenic Consequences of Sublethal Cell Death Signaling.International journal of molecular sciences · 2021Review
- Generation of TRAIL-resistant cell line models reveals distinct adaptive mechanisms for acquired resistance and re-sensitization.Oncogene · 2021Article
- Review
- TRAIL receptor-induced features of epithelial-to-mesenchymal transition increase tumour phenotypic heterogeneity: potential cell survival mechanisms.British journal of cancer · 2021Review
- Bridging Tumorigenesis and Therapy Resistance With a Non-Darwinian and Non-Lamarckian Mechanism of Adaptive Evolution.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
When clonal populations of human cells are exposed to apoptosis-inducing agents, some cells die and others survive. This fractional killing arises not from mutation but from preexisting, stochastic differences in the levels and activities of proteins regulating apoptosis. Here we examine the properties of cells that survive treatment with agonists of two distinct death receptors, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and anti-FasR antibodies. We find that "survivor" cells are highly resistant to a second ligand dose applied 1 d later. Resistance is reversible, resetting after several days of culture in the absence of death ligand. "Reset" cells appear identical to drug-naive cells with respect to death ligand sensitivity and gene expression profiles. TRAIL survivors are cross-resistant to activators of FasR and vice versa and exhibit an NF-κB-dependent inflammatory phenotype. Remarkably, reversible resistance is induced in the absence of cell death when caspase inhibitors are present and can be sustained for 1 wk or more, also without cell death, by periodic ligand exposure. Thus stochastic differences in cell state can have sustained consequences for sen-sitivity to prodeath ligands and acquisition of proinflammatory phenotypes. The important role played by periodicity in TRAIL exposure for induction of opposing apoptosis and survival mechanisms has implications for the design of optimal therapeutic agents and protocols.
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