Complex Systems Biology Approach in Connecting PI3K-Akt and NF-κB Pathways in Prostate Cancer
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 26, 2019
- Source ID
- 10.3390/cells8030201
Entities
People
- Eswar Shankar
- Jayant Avva
- Meenakshi Shukla
- Michael Weis
- Sanjay Gupta
- Sanjeev Shukla
- Sree Sreenath
Organizations
- United States Department of Defense