Journal
CELLS
Volume 8, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/cells8030201
Keywords
NF-kappa B; PI3K; Akt; systems biology
Categories
Funding
- Department of Defense [W81XWH-15-1-0558]
- Presidential Research Initiative
- VA Merit Review [1I01BX002494]
- Case Provost Opportunity funds for the Systems Biology Center of Excellence Initiative
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Phosphatidylinositol 3 '-OH kinase (PI3K)-Akt and transcription factor NF-kappa B are important molecules involved in the regulation of cell proliferation, apoptosis, and oncogenesis. Both PI3K-Akt and Nuclear Factor-kappaB (NF-kappa B) are involved in the development and progression of prostate cancer, however, the crosstalk and molecules connecting these pathway remains unclear. A multilevel system representation of the PI3K-Akt and NF-kappa B pathways was constructed to determine which signaling components contribute to adaptive behavior and coordination. In silico experiments conducted using PI3K-Akt and NF-kappa B, mathematical models were modularized using biological functionality and were validated using a cell culture system. Our analysis demonstrates that a component representing the I kappa B kinase (IKK) complex can coordinate these two pathways. It is expected that interruption of this molecule could represent a potential therapeutic target for prostate cancer.
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