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

Publication ,  Journal Article
Chifman, J; Arat, S; Deng, Z; Lemler, E; Pino, JC; Harris, LA; Kochen, MA; Lopez, CF; Akman, SA; Torti, FM; Torti, SV; Laubenbacher, R
Published in: PLoS computational biology
February 2017

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.

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Published In

PLoS computational biology

DOI

EISSN

1553-7358

ISSN

1553-734X

Publication Date

February 2017

Volume

13

Issue

2

Start / End Page

e1005352

Related Subject Headings

  • ras Proteins
  • Tumor Cells, Cultured
  • Signal Transduction
  • Models, Biological
  • Iron Regulatory Protein 2
  • Iron
  • Humans
  • Female
  • Epithelial Cells
  • Computer Simulation
 

Citation

APA
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ICMJE
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Chifman, J., Arat, S., Deng, Z., Lemler, E., Pino, J. C., Harris, L. A., … Laubenbacher, R. (2017). Activated Oncogenic Pathway Modifies Iron Network in Breast Epithelial Cells: A Dynamic Modeling Perspective. PLoS Computational Biology, 13(2), e1005352. https://doi.org/10.1371/journal.pcbi.1005352
Chifman, Julia, Seda Arat, Zhiyong Deng, Erica Lemler, James C. Pino, Leonard A. Harris, Michael A. Kochen, et al. “Activated Oncogenic Pathway Modifies Iron Network in Breast Epithelial Cells: A Dynamic Modeling Perspective.PLoS Computational Biology 13, no. 2 (February 2017): e1005352. https://doi.org/10.1371/journal.pcbi.1005352.
Chifman J, Arat S, Deng Z, Lemler E, Pino JC, Harris LA, et al. Activated Oncogenic Pathway Modifies Iron Network in Breast Epithelial Cells: A Dynamic Modeling Perspective. PLoS computational biology. 2017 Feb;13(2):e1005352.
Chifman, Julia, et al. “Activated Oncogenic Pathway Modifies Iron Network in Breast Epithelial Cells: A Dynamic Modeling Perspective.PLoS Computational Biology, vol. 13, no. 2, Feb. 2017, p. e1005352. Epmc, doi:10.1371/journal.pcbi.1005352.
Chifman J, Arat S, Deng Z, Lemler E, Pino JC, Harris LA, Kochen MA, Lopez CF, Akman SA, Torti FM, Torti SV, Laubenbacher R. Activated Oncogenic Pathway Modifies Iron Network in Breast Epithelial Cells: A Dynamic Modeling Perspective. PLoS computational biology. 2017 Feb;13(2):e1005352.

Published In

PLoS computational biology

DOI

EISSN

1553-7358

ISSN

1553-734X

Publication Date

February 2017

Volume

13

Issue

2

Start / End Page

e1005352

Related Subject Headings

  • ras Proteins
  • Tumor Cells, Cultured
  • Signal Transduction
  • Models, Biological
  • Iron Regulatory Protein 2
  • Iron
  • Humans
  • Female
  • Epithelial Cells
  • Computer Simulation