ArticleThe Journal of biological chemistry2012
Systems analysis of cancer cell heterogeneity in caspase-dependent apoptosis subsequent to mitochondrial outer membrane permeabilization.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 30 citations in OpenAlex.
- Live-cell imaging and mathematical analysis of the "community effect" in apoptosis.Apoptosis : an international journal on programmed cell death · 2023Article
- Two-level modeling approach to identify the regulatory dynamics capturing drug response heterogeneity in single-cells.Scientific reports · 2021Article
- The apoptosome molecular timer synergises with XIAP to suppress apoptosis execution and contributes to prognosticating survival in colorectal cancer.Cell death and differentiation · 2020Article
- System-based approaches as prognostic tools for glioblastoma.BMC cancer · 2019Review
- Simulating and predicting cellular and in vivo responses of colon cancer to combined treatment with chemotherapy and IAP antagonist Birinapant/TL32711.Cell death and differentiation · 2018Article
- Article
- Doxorubicin-induced chronic dilated cardiomyopathy-the apoptosis hypothesis revisited.Journal of molecular medicine (Berlin, Germany) · 2017Review
- Die-hard survivors: heterogeneity in apoptotic thresholds may underlie chemoresistance.Expert review of anticancer therapy · 2015Article
- A systems biology analysis of apoptosome formation and apoptosis execution supports allosteric procaspase-9 activation.The Journal of biological chemistry · 2014Article
- From computational modelling of the intrinsic apoptosis pathway to a systems-based analysis of chemotherapy resistance: achievements, perspectives and challenges in systems medicine.Cell death & disease · 2014Review
- Harnessing system models of cell death signalling for cytotoxic chemotherapy: towards personalised medicine approaches?Journal of molecular medicine (Berlin, Germany) · 2014Review
- Understanding health and disease with multidimensional single-cell methods.Journal of physics. Condensed matter : an Institute of Physics journal · 2014Review
- Key regulators of apoptosis execution as biomarker candidates in melanoma.Molecular & cellular oncologyReview
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deregulation of apoptosis is a hallmark of carcinogenesis. We here combine live cell imaging and systems modeling to investigate caspase-dependent apoptosis execution subsequent to mitochondrial outer membrane permeabilization (MOMP) in several cancer cell lines. We demonstrate that, although most cell lines that underwent MOMP also showed robust and fast activation of executioner caspases and apoptosis, the colorectal cancer cell lines LoVo and HCT-116 Smac(-/-), similar to X-linked inhibitor of apoptosis protein (XIAP)-overexpressing HeLa (HeLa XIAP(Adv)) cells, only showed delayed and often no caspase activation, suggesting apoptosis impairment subsequent to MOMP. Employing APOPTO-CELL, a recently established model of apoptosis subsequent to MOMP, this impairment could be understood by studying the systemic interaction of five proteins that are present in the apoptosis pathway subsequent to MOMP. Using APOPTO-CELL as a tool to study detailed molecular mechanisms during apoptosis execution in individual cell lines, we demonstrate that caspase-9 was the most important regulator in DLD-1, HCT-116, and HeLa cells and identified additional cell line-specific co-regulators. Developing and applying a computational workflow for parameter screening, systems modeling identified that apoptosis execution kinetics are more robust against changes in reaction kinetics in HCT-116 and HeLa than in DLD-1 cells. Our systems modeling study is the first to draw attention to the variability in cell specific protein levels and reaction rates and to the emergent effects of such variability on the efficiency of apoptosis execution and on apoptosis impairment subsequent to MOMP.
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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.