ArticleCell death and differentiation2013
The DNA damage checkpoint precedes activation of ARF in response to escalating oncogenic stress during tumorigenesis.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 59 citations in OpenAlex.
- Dysregulated expression of the tumor suppressor p14ARF in cancer provides an effective target for TCR-T cell therapeutics.Journal for immunotherapy of cancer · 2026Article
- Complex p53 dynamics regulated by miR-125b in cellular responses to reactive oxidative stress and DNA damage.Briefings in bioinformatics · 2024Article
- Synthetic lethal interaction between WEE1 and PKMYT1 is a target for multiple low-dose treatment of high-grade serous ovarian carcinoma.NAR cancer · 2023Article
- Interplay of Developmental Hippo-Notch Signaling Pathways with the DNA Damage Response in Prostate Cancer.Cells · 2022Review
- Cannabidiol-induced activation of the metallothionein pathway impedes anticancer effects of disulfiram and its metabolite CuET.Molecular oncology · 2022Article
- RNA-interference screen for p53 regulators unveils a role of WDR75 in ribosome biogenesis.Cell death and differentiation · 2022Article
- Mesenchymal Stem Cell Senescence and Osteogenesis.Medicina (Kaunas, Lithuania) · 2021Review
- Mechanisms and Regulation of Cellular Senescence.International journal of molecular sciences · 2021Review
- Non-Canonical Functions of the ARF Tumor Suppressor in Development and Tumorigenesis.Biomolecules · 2021Review
- Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype.Frontiers in cell and developmental biology · 2021Review
- Role of genomic instability in human carcinogenesis.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Integrating the DNA damage and protein stress responses during cancer development and treatment.The Journal of pathology · 2018Review
- Oncogene-induced senescence and its evasion in a mouse model of thyroid neoplasia.Molecular and cellular endocrinology · 2018Article
- A prototypical non-malignant epithelial model to study genome dynamics and concurrently monitor micro-RNAs and proteins in situ during oncogene-induced senescence.BMC genomics · 2018Article
- MYC and RAS are unable to cooperate in overcoming cellular senescence and apoptosis in normal human fibroblasts.Cell cycle (Georgetown, Tex.) · 2018Article
- Monitoring Autophagy Immunohistochemically and Ultrastructurally during Human Head and Neck Carcinogenesis. Relationship with the DNA Damage Response Pathway.International journal of molecular sciences · 2017Article
- Article
- WSB1 overcomes oncogene-induced senescence by targeting ATM for degradation.Cell research · 2017Article
- Genetic Variability as a Regulator of TLR4 and NOD Signaling in Response to Bacterial Driven DNA Damage Response (DDR) and Inflammation: Focus on the Gastrointestinal (GI) Tract.Frontiers in genetics · 2017Review
- Inflammation, DNA Damage,Frontiers in genetics · 2017Review
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22 authors at 9 institutions in 5 countries.
Funding
Abstract
Oncogenic stimuli trigger the DNA damage response (DDR) and induction of the alternative reading frame (ARF) tumor suppressor, both of which can activate the p53 pathway and provide intrinsic barriers to tumor progression. However, the respective timeframes and signal thresholds for ARF induction and DDR activation during tumorigenesis remain elusive. Here, these issues were addressed by analyses of mouse models of urinary bladder, colon, pancreatic and skin premalignant and malignant lesions. Consistently, ARF expression occurred at a later stage of tumor progression than activation of the DDR or p16(INK4A), a tumor-suppressor gene overlapping with ARF. Analogous results were obtained in several human clinical settings, including early and progressive lesions of the urinary bladder, head and neck, skin and pancreas. Mechanistic analyses of epithelial and fibroblast cell models exposed to various oncogenes showed that the delayed upregulation of ARF reflected a requirement for a higher, transcriptionally based threshold of oncogenic stress, elicited by at least two oncogenic 'hits', compared with lower activation threshold for DDR. We propose that relative to DDR activation, ARF provides a complementary and delayed barrier to tumor development, responding to more robust stimuli of escalating oncogenic overload.
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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.