ArticleScience advances2019
Efficient apoptosis requires feedback amplification of upstream apoptotic signals by effector caspase-3 or -7.
Article in Science advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
127 citing papers in PubMed, 1 synthesis or guideline pooled it, 264 citations in OpenAlex.
- Top 100 most-cited articles on apoptosis of non-small cell lung cancer over the past two decades: a bibliometrics analysis.Frontiers in immunology · 2024Pooled it
- Age-dependent mitochondrial toxicity in renal stem cells: A precise 3D silk matrix model.Genes & diseases · 2026Article
- Apoptosis gene expression analysis identifies biologically distinct AML clusters and BIK as an independent prognostic marker.Annals of hematology · 2026Article
- Evasion of cell death despite mitochondrial outer membrane permeabilization: an oncogenic outcome of apoptosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Paeonol's protective effects on H9C2 cells against hypoxia/ reoxygenation injury through the hypoxia-inducible factor 1-alpha/B-cell lymphoma-2/adenovirus E1B 19 kDa interacting protein 3 signaling pathway.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- Engineering Urchin-Shaped Copper Nanospheres for Synergistic Apoptosis and Cuproptosis via Oxidative Stress Amplification in Cancer Therapy.Advanced healthcare materials · 2026Article
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- A clinical-stage oncology compound selectively targets drug-resistant cancers.bioRxiv : the preprint server for biology · 2026Article
- Characterization of Large Extracellular Vesicles Released by Apoptotic and Pyroptotic Cells.International journal of molecular sciences · 2026Article
- Rewiring of host cell signaling in chikungunya virus infection: a mechanism for pathogenesis and therapeutic approaches.Archives of microbiology · 2026Review
- Loss of Cathepsin K Impairs Collagen Biogenesis and Enhances Actin Polymerization in Trabecular Meshwork.Investigative ophthalmology & visual science · 2026Article
- Mammalian innate antiviral defenses: beyond interferon.Journal of virology · 2025Review
- Three decades of caspases and RIPKs in life and death.Human molecular genetics · 2025Review
- PANoptosis in cancer: molecular mechanisms and therapeutic potential.Cancer gene therapy · 2025Review
- HSV-1 hijacks mitochondrial dynamics: potential molecular mechanisms linking viral infection to neurodegenerative disorders.Apoptosis : an international journal on programmed cell death · 2025Review
- Article
- The potential of probiotic derivatives of Bacillus coagulans Hammer on induction of apoptosis in colorectal adenocarcinoma cell line in vitro.BMC complementary medicine and therapies · 2025Article
- Antibacterial and anticancer activity of multifunctional iron-based magnetic nanoparticles against urinary tract infection and cystitis-related bacterial strains and bladder cancer cells.Biomedical engineering letters · 2025Article
- GD3 synthase drives resistance to p53-induced apoptosis in breast cancer by modulating mitochondrial function.Oncogene · 2025Article
- Intracellular Formation of Synthetic Peptide Nanostructures Causes Mitochondrial Disruption and Cell Death in Tumor Spheroids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
67 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apoptosis is a complex multi-step process driven by caspase-dependent proteolytic cleavage cascades. Dysregulation of apoptosis promotes tumorigenesis and limits the efficacy of chemotherapy. To assess the complex interactions among caspases during apoptosis, we disrupted caspase-8, -9, -3, -7, or -6 and combinations thereof, using CRISPR-based genome editing in living human leukemia cells. While loss of apical initiator caspase-8 or -9 partially blocked extrinsic or intrinsic apoptosis, respectively, only combined loss of caspase-3 and -7 fully inhibited both apoptotic pathways, with no discernible effect of caspase-6 deficiency alone or in combination. Caspase-3/7 double knockout cells exhibited almost complete inhibition of caspase-8 or -9 activation. Furthermore, deletion of caspase-3 and -7 decreased mitochondrial depolarization and cytochrome c release upon apoptosis activation. Thus, activation of effector caspase-3 or -7 sets off explosive feedback amplification of upstream apoptotic events, which is a key feature of apoptotic signaling essential for efficient apoptotic cell death.
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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.