Mechanistic Model of Signaling Dynamics Across an Epithelial Mesenchymal Transition
| العنوان: | Mechanistic Model of Signaling Dynamics Across an Epithelial Mesenchymal Transition |
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| المؤلفون: | Bernd Bodenmiller, Nevena Zivanovic, Xiao-Kang Lun, James D Wade, Eberhard O. Voit |
| المساهمون: | University of Zurich, Voit, Eberhard O, Bodenmiller, Bernd |
| المصدر: | Frontiers in Physiology, Vol 11 (2020) Frontiers in Physiology, 11 Frontiers in Physiology |
| مصطلحات موضوعية: | MAPK/ERK pathway, Physiology, Systems biology, Cell, 610 Medicine & health, Biology, lcsh:Physiology, 03 medical and health sciences, 0302 clinical medicine, 2737 Physiology (medical), computational biology, epithelial-to-mesenchymal transition (EMT), systems biology, ordinary differential equations, kinetic model, ERK pathway, AKT pathway, single cell modeling, Physiology (medical), medicine, Mass cytometry, Epithelial–mesenchymal transition, Protein kinase B, PI3K/AKT/mTOR pathway, Original Research, 030304 developmental biology, 0303 health sciences, lcsh:QP1-981, 1314 Physiology, Cell biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Signal transduction, 11493 Department of Quantitative Biomedicine |
| الوصف: | Intracellular signaling pathways are at the core of cellular information processing. The states of these pathways and their inputs determine signaling dynamics and drive cell function. Within a cancerous tumor, many combinations of cell states and microenvironments can lead to dramatic variations in responses to treatment. Network rewiring has been thought to underlie these context-dependent differences in signaling; however, from a biochemical standpoint, rewiring of signaling networks should not be a prerequisite for heterogeneity in responses to stimuli. Here we address this conundrum by analyzing an in vitro model of the epithelial mesenchymal transition (EMT), a biological program implicated in increased tumor invasiveness, heterogeneity, and drug resistance. We used mass cytometry to measure EGF signaling dynamics in the ERK and AKT signaling pathways before and after induction of EMT in Py2T murine breast cancer cells. Analysis of the data with standard network inference methods suggested EMT-dependent network rewiring. In contrast, use of a modeling approach that adequately accounts for single-cell variation demonstrated that a single reaction-based pathway model with constant structure and near-constant parameters is sufficient to represent differences in EGF signaling across EMT. This result indicates that rewiring of the signaling network is not necessary for heterogeneous responses to a signal and that unifying reaction-based models should be employed for characterization of signaling in heterogeneous environments, such as cancer. Frontiers in Physiology, 11 ISSN:1664-042X |
| وصف الملف: | application/application/pdf; fphys-11-579117.pdf - application/pdf |
| اللغة: | English |
| تدمد: | 1664-042X |
| DOI: | 10.3389/fphys.2020.579117 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fd6767239b9912f01a346d5847db47efTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fd6767239b9912f01a346d5847db47ef |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1664042X |
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| DOI: | 10.3389/fphys.2020.579117 |