Complex Systems Biology Approach in Connecting PI3K-Akt and NF-κB Pathways in Prostate Cancer

• Published in: Cells (Basel, Switzerland) Vol. 8; no. 3; p. 201
• Main Authors: Shankar, Eswar, Weis, Michael C, Avva, Jayant, Shukla, Sanjeev, Shukla, Meenakshi, Sreenath, Sree N, Gupta, Sanjay
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.02.2019; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Apoptosis; Biology; Cell culture; Cell growth; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Computer Simulation; Epidermal growth factor; Epidermal Growth Factor - pharmacology; Gene expression; Humans; I-kappa B Kinase - metabolism; I-kappa B Proteins - metabolism; Kinases; Laboratories; Male; Mathematical models; Medical prognosis; NF-kappa B - metabolism; NF-κB; NF-κB protein; Ordinary differential equations; Phosphatase; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Phosphorylation - drug effects; PI3K/Akt; Prostate cancer; Prostatic Neoplasms - metabolism; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; Systems Biology; Transcription factors; Transcription, Genetic - drug effects; Tumorigenesis; United States > US; systems biology; NF-κB; PI3K/Akt
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells8030201

Phosphatidylinositol 3'-OH kinase (PI3K)-Akt and transcription factor NF-κB are important molecules involved in the regulation of cell proliferation, apoptosis, and oncogenesis. Both PI3K-Akt and Nuclear Factor-kappaB (NF-κB) 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-κB pathways was constructed to determine which signaling components contribute to adaptive behavior and coordination. In silico experiments conducted using PI3K-Akt and NF-κB, mathematical models were modularized using biological functionality and were validated using a cell culture system. Our analysis demonstrates that a component representing the IκB 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.