ArticleCell cycle (Georgetown, Tex.)2013
DNA damage causes TP53-dependent coupling of self-renewal and senescence pathways in embryonal carcinoma cells.
Article in Cell cycle (Georgetown, Tex.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Etiology of polyploid giant cancer cells: a new frontier in cancer biology.Cancer cell international · 2026Review
- Article
- AMPK/MTOR/TP53 Signaling Pathway Regulation by Calcitonin Gene-Related Peptide Reduces Oxygen-Induced Lung Damage in Neonatal Rats through Autophagy Promotion.Inflammation · 2024Article
- The Importance of Monitoring Non-clonal Chromosome Aberrations (NCCAs) in Cancer Research.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Review
- High Hemin Concentration Induces Escape from Senescence of Normoxic and Hypoxic Colon Cancer Cells.Cancers · 2022Article
- Sphingolipids in embryonic development, cell cycle regulation, and stemness - Implications for polyploidy in tumors.Seminars in cancer biology · 2022Review
- CD44+ and CD133+ Non-Small Cell Lung Cancer Cells Exhibit DNA Damage Response Pathways and Dormant Polyploid Giant Cancer Cell Enrichment Relating to Their p53 Status.International journal of molecular sciences · 2022Article
- Review
- "Mitotic Slippage" and Extranuclear DNA in Cancer Chemoresistance: A Focus on Telomeres.International journal of molecular sciences · 2020Article
- The Phenoxyphenol Compound 4-HPPP Selectively Induces Antiproliferation Effects and Apoptosis in Human Lung Cancer Cells through Aneupolyploidization and ATR DNA Repair Signaling.Oxidative medicine and cellular longevity · 2020Article
- Article
- DNA methylation of the Oct4A enhancers in embryonal carcinoma cells after etoposide treatment is associated with alternative splicing and altered pluripotency in reversibly senescent cells.Cell cycle (Georgetown, Tex.) · 2018Article
- Nucleolar aggresomes mediate release of pericentric heterochromatin and nuclear destruction of genotoxically treated cancer cells.Nucleus (Austin, Tex.) · 2017Article
- Molecular Genetic Analysis of Human Endometrial Mesenchymal Stem Cells That Survived Sublethal Heat Shock.Stem cells international · 2017Article
- Disentangling the aneuploidy and senescence paradoxes: a study of triploid breast cancers non-responsive to neoadjuvant therapy.Histochemistry and cell biology · 2016Article
- Why it is crucial to analyze non clonal chromosome aberrations or NCCAs?Molecular cytogenetics · 2016Article
- Polyploidy Formation in Doxorubicin-Treated Cancer Cells Can Favor Escape from Senescence.Neoplasia (New York, N.Y.) · 2015Article
- Article
- Non-genetic cancer cell plasticity and therapy-induced stemness in tumour relapse: 'What does not kill me strengthens me'.British journal of cancer · 2015Review
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies have highlighted an apparently paradoxical link between self-renewal and senescence triggered by DNA damage in certain cell types. In addition, the finding that TP53 can suppress senescence has caused a re-evaluation of its functional role in regulating these outcomes. To investigate these phenomena and their relationship to pluripotency and senescence, we examined the response of the TP53-competent embryonal carcinoma (EC) cell line PA-1 to etoposide-induced DNA damage. Nuclear POU5F1/OCT4A and P21CIP1 were upregulated in the same cells following etoposide-induced G 2M arrest. However, while accumulating in the karyosol, the amount of OCT4A was reduced in the chromatin fraction. Phosphorylated CHK2 and RAD51/γH2AX-positive nuclear foci, overexpression of AURORA B kinase and moderate macroautophagy were evident. Upon release from G 2M arrest, cells with repaired DNA entered mitoses, while the cells with persisting DNA damage remained at this checkpoint or underwent mitotic slippage and gradually senesced. Reduction of TP53 using sh- or si-RNA prevented the upregulation of OCT4A and P21CIP1 and increased DNA damage. Subsequently, mitoses, micronucleation and senescence were all enhanced after TP53 reduction with senescence confirmed by upregulation of CDKN2A/P16INK4A and increased sa-β-galactosidase positivity. Those mitoses enhanced by TP53 silencing were shown to be multicentrosomal and multi-polar, containing fragmented and highly deranged chromosomes, indicating a loss of genome integrity. Together, these data suggest that TP53-dependent coupling of self-renewal and senescence pathways through the DNA damage checkpoint provides a mechanism for how embryonal stem cell-like EC cells safeguard DNA integrity, genome stability and ultimately the fidelity of self-renewal.
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