ArticleCell death & disease2022
Spontaneous activity of the mitochondrial apoptosis pathway drives chromosomal defects, the appearance of micronuclei and cancer metastasis through the Caspase-Activated DNAse.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Evasion of cell death despite mitochondrial outer membrane permeabilization: an oncogenic outcome of apoptosis.Apoptosis : an international journal on programmed cell death · 2026Review
- The second mitochondrial activator of caspases (SMAC) regulates growth, inflammation and mitochondrial integrity in cancer cells.Cell death and differentiation · 2026Article
- NOXA/MCL-1 axis determines cell-death decision between apoptosis and a GSDME-dependent cell death associated with production of inflammatory cytokines upon treatment of breast cancer cells with antimitotics.Cell death & disease · 2026Article
- DNA fragmentation factor B suppresses interferon to enable cancer persister cell regrowth.Nature cell biology · 2025Article
- PUMA reduces FASN ubiquitination to promote lipid accumulation and tumor progression in human clear cell renal cell carcinoma.Cell death & disease · 2025Article
- Arctigenin Suppresses MelanomaCurrent cancer drug targets · 2025Article
- Caspase-Activated DNase localizes to cancer causing translocation breakpoints during cell differentiation.bioRxiv : the preprint server for biology · 2024Article
- Human Umbilical Cord Mesenchymal Stem Cells Prevent Steroid-Induced Avascular Necrosis of the Femoral Head by Modulating Cellular Autophagy.Biomedicines · 2024Article
- Mitochondria and cell death.Nature cell biology · 2024Review
- The caspase-activated DNase promotes cellular senescence.The EMBO journal · 2024Article
- The Caspase-Activated DNase drives inflammation and contributes to defense against viral infection.Cell death and differentiation · 2024Article
- At the Crossroads of the cGAS-cGAMP-STING Pathway and the DNA Damage Response: Implications for Cancer Progression and Treatment.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Mechanisms of metabolic stress induced cell death of human oligodendrocytes: relevance for progressive multiple sclerosis.Acta neuropathologica communications · 2023Article
- Non-lethal outcomes of engaging regulated cell death pathways in cancer.Nature cancer · 2023Review
- Sub-lethal signals in the mitochondrial apoptosis apparatus: pernicious by-product or physiological event?Cell death and differentiation · 2023Review
- Micronuclei in Circulating Tumor Associated Macrophages Predicts Progression in Advanced Colorectal Cancer.Biomedicines · 2022Article
- Pattern Recognition Receptors of Nucleic Acids Can Cause Sublethal Activation of the Mitochondrial Apoptosis Pathway during Viral Infection.Journal of virology · 2022Article
- Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis.The Journal of cell biology · 2022Review
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Micronuclei are DNA-containing structures separate from the nucleus found in cancer cells. Micronuclei are recognized by the immune sensor axis cGAS/STING, driving cancer metastasis. The mitochondrial apoptosis apparatus can be experimentally triggered to a non-apoptotic level, and this can drive the appearance of micronuclei through the Caspase-activated DNAse (CAD). We tested whether spontaneously appearing micronuclei in cancer cells are linked to sub-lethal apoptotic signals. Inhibition of mitochondrial apoptosis or of CAD reduced the number of micronuclei in tumor cell lines as well as the number of chromosomal misalignments in tumor cells and intestinal organoids. Blockade of mitochondrial apoptosis or deletion of CAD reduced, while experimental activation CAD, STING-dependently, enhanced aggressive growth of tumor cells in vitro. Deletion of CAD from human cancer cells reduced metastasis in xenograft models. CAD-deficient cells displayed a substantially altered gene-expression profile, and a CAD-associated gene expression 'signature' strongly predicted survival in cancer patients. Thus, low-level activity in the mitochondrial apoptosis apparatus operates through CAD-dependent gene-induction and STING-activation and has substantial impact on metastasis in cancer.
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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.