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Activated Oncogenic Pathway Modifies Iron Network in Breast Epithelial Cells: A Dynamic Modeling Perspective

Chifman, Julia ; Arat, Seda ; Deng, Zhiyong ; Lemler, Erica ; Pino, James C ; Harris, Leonard A ; Kochen, Michael A ; Lopez, Carlos F ; Akman, Steven A ; Torti, Frank M ; Torti, Suzy V ; Laubenbacher, Reinhard Asthagiri, Anand R.

PLoS computational biology, 2017-02, Vol.13 (2), p.e1005352-e1005352 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Activated Oncogenic Pathway Modifies Iron Network in Breast Epithelial Cells: A Dynamic Modeling Perspective
Autor: Chifman, Julia ; Arat, Seda ; Deng, Zhiyong ; Lemler, Erica ; Pino, James C ; Harris, Leonard A ; Kochen, Michael A ; Lopez, Carlos F ; Akman, Steven A ; Torti, Frank M ; Torti, Suzy V ; Laubenbacher, Reinhard
Asthagiri, Anand R.
Assuntos: Adaptation, Physiological ; Animals ; Biology and Life Sciences ; Biophysics ; Breast - metabolism ; Breast - pathology ; Breast cancer ; Cell Transformation, Neoplastic - metabolism ; Colleges & universities ; Computer Simulation ; Epithelial cells ; Epithelial Cells - metabolism ; Epithelial Cells - pathology ; Experiments ; Female ; Health aspects ; Homeostasis ; Humans ; Informatics ; Iron (Nutrient) ; Iron - metabolism ; Iron in the body ; Iron Regulatory Protein 2 - metabolism ; Laboratories ; Mathematical models ; Medicine ; Medicine and Health Sciences ; Metabolism ; Models, Biological ; Molecular biology ; Oxidative stress ; Physical Sciences ; Physiological aspects ; ras Proteins - metabolism ; Rodents ; Signal Transduction ; Stress response ; Tumor Cells, Cultured
É parte de: PLoS computational biology, 2017-02, Vol.13 (2), p.e1005352-e1005352
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
The authors have declared that no competing interests exist.
Conceived and designed the experiments: ZD EL.Performed the experiments: ZD EL.Analyzed the data: JC SA.Contributed reagents/materials/analysis tools: SVT FMT SAA RL.Wrote the paper: JC SA RL.Developed the concept of the project: JC RL. Led network construction, mathematical model development and attractor analysis: JC SA. Designed and wrote the codes for model simulations and attractor analysis: JC SA JCP LAH MAK CFL. Directed the project: RL.
Descrição: Dysregulation of iron metabolism in cancer is well documented and it has been suggested that there is interdependence between excess iron and increased cancer incidence and progression. In an effort to better understand the linkages between iron metabolism and breast cancer, a predictive mathematical model of an expanded iron homeostasis pathway was constructed that includes species involved in iron utilization, oxidative stress response and oncogenic pathways. The model leads to three predictions. The first is that overexpression of iron regulatory protein 2 (IRP2) recapitulates many aspects of the alterations in free iron and iron-related proteins in cancer cells without affecting the oxidative stress response or the oncogenic pathways included in the model. This prediction was validated by experimentation. The second prediction is that iron-related proteins are dramatically affected by mitochondrial ferritin overexpression. This prediction was validated by results in the pertinent literature not used for model construction. The third prediction is that oncogenic Ras pathways contribute to altered iron homeostasis in cancer cells. This prediction was validated by a combination of simulation experiments of Ras overexpression and catalase knockout in conjunction with the literature. The model successfully captures key aspects of iron metabolism in breast cancer cells and provides a framework upon which more detailed models can be built.
Editor: United States: Public Library of Science
Idioma: Inglês

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Activated Oncogenic Pathway Modifies Iron Network in Breast Epithelial Cells: A Dynamic Modeling Perspective

Chifman, Julia ; Arat, Seda ; Deng, Zhiyong ; Lemler, Erica ; Pino, James C ; Harris, Leonard A ; Kochen, Michael A ; Lopez, Carlos F ; Akman, Steven A ; Torti, Frank M ; Torti, Suzy V ; Laubenbacher, Reinhard Asthagiri, Anand R.

United States: Public Library of Science

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