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

Eswar Shankar,Meenakshi Shukla,Jayant Avva,Sanjay Gupta,Sree Sreenath,Michael Weis,Sanjeev Shukla

doi:10.3390/cells8030201

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.

Highlights

Prostate cancer remains the third most common cancer worldwide with over one million new cases detected annually; it is the second leading cause of cancer-related deaths in men in the UnitedStates [1,2]
We further demonstrated the involvement of these molecules in prostate cancer using an autochthonous transgenic mouse model [28]
This exercise resulted in a complete model of epidermal growth factor (EGF) activated Phosphatidylinositol 3 -OH kinase (PI3K)-Akt and NF-κB

Summary

Introduction

Prostate cancer remains the third most common cancer worldwide with over one million new cases detected annually; it is the second leading cause of cancer-related deaths in men in the UnitedStates [1,2]. Prostate cancer remains the third most common cancer worldwide with over one million new cases detected annually; it is the second leading cause of cancer-related deaths in men in the United. According to an estimate by the American Cancer Society, approximately 174,650 new prostate cancer cases will be diagnosed and 31,620 deaths will occur in the United States in. Prostate cancer is a heterogeneous disease and often remains indolent where patients remain asymptomatic for years. It has been difficult, to discriminate between treatable and non-treatable tumors as concerns have been raised of increased over-diagnosis and unnecessary treatment [4]. There is an urgent need to identify precise targets to determine appropriate treatments

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Results

Conclusion