ArticleMolecular systems biology2012
Combined experimental and computational analysis of DNA damage signaling reveals context-dependent roles for Erk in apoptosis and G1/S arrest after genotoxic stress.
Article in Molecular systems biology, 2012. 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, 2 citations in OpenAlex.
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- CRISPR screens reveal convergent targeting strategies against evolutionarily distinct chemoresistance in cancer.Nature communications · 2024Article
- Biphasic JNK-Erk signaling separates the induction and maintenance of cell senescence after DNA damage induced by topoisomerase II inhibition.Cell systems · 2023Article
- A lineage tree-based hidden Markov model quantifies cellular heterogeneity and plasticity.Communications biology · 2022Article
- Review
- The injury response to DNA damage in live tumor cells promotes antitumor immunity.Science signaling · 2021Article
- Integrative Multi-Omics Approaches in Cancer Research: From Biological Networks to Clinical Subtypes.Molecules and cells · 2021Review
- Platelet Microparticles Decrease Daunorubicin-Induced DNA Damage and Modulate Intrinsic Apoptosis in THP-1 Cells.International journal of molecular sciences · 2021Article
- Dual functionalized brain-targeting nanoinhibitors restrain temozolomide-resistant glioma via attenuating EGFR and MET signaling pathways.Nature communications · 2020Article
- MAPKAP Kinase-2 Drives Expression of Angiogenic Factors by Tumor-Associated Macrophages in a Model of Inflammation-Induced Colon Cancer.Frontiers in immunology · 2020Article
- Robust latent-variable interpretation of in vivo regression models by nested resampling.Scientific reports · 2019Article
- Use of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Preclinical Cancer Drug Cardiotoxicity Testing: A Scientific Statement From the American Heart Association.Circulation research · 2019Review
- Modeling of Cisplatin-Induced Signaling Dynamics in Triple-Negative Breast Cancer Cells Reveals Mediators of Sensitivity.Cell reports · 2019Article
- EGF receptor and PKCδ kinase activate DNA damage-induced pro-survival and pro-apoptotic signaling via biphasic activation of ERK and MSK1 kinases.The Journal of biological chemistry · 2019Article
- Lysophosphatidic acid type 2 receptor agonists in targeted drug development offer broad therapeutic potential.Journal of lipid research · 2019Review
- A Loss of Epigenetic Control Can Promote Cell Death through Reversing the Balance of Pathways in a Signaling Network.Molecular cell · 2018Article
- Netrin-1 Prevents Rat Primary Cortical Neurons from Apoptosis via the DCC/ERK Pathway.Frontiers in cellular neuroscience · 2017Article
- A novel mathematical model of ATM/p53/NF- κB pathways points to the importance of the DDR switch-off mechanisms.BMC systems biology · 2016Article
- TNF-insulin crosstalk at the transcription factor GATA6 is revealed by a model that links signaling and transcriptomic data tensors.Science signaling · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Following DNA damage, cells display complex multi-pathway signaling dynamics that connect cell-cycle arrest and DNA repair in G1, S, or G2/M phase with phenotypic fate decisions made between survival, cell-cycle re-entry and proliferation, permanent cell-cycle arrest, or cell death. How these phenotypic fate decisions are determined remains poorly understood, but must derive from integrating genotoxic stress signals together with inputs from the local microenvironment. To investigate this in a systematic manner, we undertook a quantitative time-resolved cell signaling and phenotypic response study in U2OS cells receiving doxorubicin-induced DNA damage in the presence or absence of TNFα co-treatment; we measured key nodes in a broad set of DNA damage signal transduction pathways along with apoptotic death and cell-cycle regulatory responses. Two relational modeling approaches were then used to identify network-level relationships between signals and cell phenotypic events: a partial least squares regression approach and a complementary new technique which we term 'time-interval stepwise regression.' Taken together, the results from these analysis methods revealed complex, cytokine-modulated inter-relationships among multiple signaling pathways following DNA damage, and identified an unexpected context-dependent role for Erk in both G1/S arrest and apoptotic cell death following treatment with this commonly used clinical chemotherapeutic drug.
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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.