ArticleFrontiers in physiology2012
Heterogeneous kinetics of AKT signaling in individual cells are accounted for by variable protein concentration.
Article in Frontiers in physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Activity and safety of crizotinib in patients with advanced clear-cell sarcoma with MET alterations: European Organization for Research and Treatment of Cancer phase II trial 90101 'CREATE'.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Trial
- The ability to sense the environment is heterogeneously distributed in cell populations.eLife · 2024Article
- Modeling Cellular Signaling Variability Based on Single-Cell Data: The TGFβ-SMAD Signaling Pathway.Methods in molecular biology (Clifton, N.J.) · 2023Review
- NF-kB in Signaling Patterns and Its Temporal Dynamics Encode/Decode Human Diseases.Life (Basel, Switzerland) · 2022Review
- Modulation of signaling cross-talk between pJNK and pAKT generates optimal apoptotic response.PLoS computational biology · 2022Article
- Pre-existing Cell States Control Heterogeneity of Both EGFR and CXCR4 Signaling.Cellular and molecular bioengineering · 2021Article
- Maximum Entropy Framework for Predictive Inference of Cell Population Heterogeneity and Responses in Signaling Networks.Cell systems · 2020Article
- Individual Cells Can Resolve Variations in Stimulus Intensity along the IGF-PI3K-AKT Signaling Axis.Cell systems · 2019Article
- Short-term cellular memory tunes the signaling responses of the chemokine receptor CXCR4.Science signaling · 2019Article
- Crosstalk in transition: the translocation of Akt.Journal of mathematical biology · 2019Article
- Getting the Akt Together: Guiding Intracellular Akt Activity by PI3K.Biomolecules · 2019Review
- Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma.NPJ systems biology and applications · 2019Article
- Modeling cell line-specific recruitment of signaling proteins to the insulin-like growth factor 1 receptor.PLoS computational biology · 2019Article
- Deciphering the Dynamical Origin of Mixed Population during Neural Stem Cell Development.Biophysical journal · 2018Article
- FoxO3 an important player in fibrogenesis and therapeutic target for idiopathic pulmonary fibrosis.EMBO molecular medicine · 2018Article
- Predictive model identifies strategies to enhance TSP1-mediated apoptosis signaling.Cell communication and signaling : CCS · 2017Article
- Modeling Cellular Noise Underlying Heterogeneous Cell Responses in the Epidermal Growth Factor Signaling Pathway.PLoS computational biology · 2016Article
- An Integrated Chemical Cytometry Method: Shining a Light on Akt Activity in Single Cells.Angewandte Chemie (International ed. in English) · 2016Article
- Conservation of protein abundance patterns reveals the regulatory architecture of the EGFR-MAPK pathway.Science signaling · 2016Article
- Investigating the Role of TNF-α and IFN-γ Activation on the Dynamics of iNOS Gene Expression in LPS Stimulated Macrophages.PloS one · 2016Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In most solid cancers, cells harboring oncogenic mutations represent only a sub-fraction of the entire population. Within this sub-fraction the expression level of mutated proteins can vary significantly due to cellular variability limiting the efficiency of targeted therapy. To address the causes of the heterogeneity, we performed a systematic analysis of one of the most frequently mutated pathways in cancer cells, the phosphatidylinositol 3 kinase (PI3K) signaling pathway. Among others PI3K signaling is activated by the hepatocyte growth factor (HGF) that regulates proliferation of hepatocytes during liver regeneration but also fosters tumor cell proliferation. HGF-mediated responses of PI3K signaling were monitored both at the single cell and cell population level in primary mouse hepatocytes and in the hepatoma cell line Hepa1_6. Interestingly, we observed that the HGF-mediated AKT responses at the level of individual cells is rather heterogeneous. However, the overall average behavior of the single cells strongly resembled the dynamics of AKT activation determined at the cell population level. To gain insights into the molecular cause for the observed heterogeneous behavior of individual cells, we employed dynamic mathematical modeling in a stochastic framework. Our analysis demonstrated that intrinsic noise was not sufficient to explain the observed kinetic behavior, but rather the importance of extrinsic noise has to be considered. Thus, distinct from gene expression in the examined signaling pathway fluctuations of the reaction rates has only a minor impact whereas variability in the concentration of the various signaling components even in a clonal cell population is a key determinant for the kinetic behavior.
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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.