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Complex Systems Biology Approach in Connecting PI3K-Akt and NF-κB Pathways in Prostate Cancer
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, howeve...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468646/ https://www.ncbi.nlm.nih.gov/pubmed/30813597 http://dx.doi.org/10.3390/cells8030201 |
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author | Shankar, Eswar Weis, Michael C. Avva, Jayant Shukla, Sanjeev Shukla, Meenakshi Sreenath, Sree N. Gupta, Sanjay |
author_facet | Shankar, Eswar Weis, Michael C. Avva, Jayant Shukla, Sanjeev Shukla, Meenakshi Sreenath, Sree N. Gupta, Sanjay |
author_sort | Shankar, Eswar |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6468646 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64686462019-04-23 Complex Systems Biology Approach in Connecting PI3K-Akt and NF-κB Pathways in Prostate Cancer Shankar, Eswar Weis, Michael C. Avva, Jayant Shukla, Sanjeev Shukla, Meenakshi Sreenath, Sree N. Gupta, Sanjay Cells Article 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. MDPI 2019-02-26 /pmc/articles/PMC6468646/ /pubmed/30813597 http://dx.doi.org/10.3390/cells8030201 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Shankar, Eswar Weis, Michael C. Avva, Jayant Shukla, Sanjeev Shukla, Meenakshi Sreenath, Sree N. Gupta, Sanjay Complex Systems Biology Approach in Connecting PI3K-Akt and NF-κB Pathways in Prostate Cancer |
title | Complex Systems Biology Approach in Connecting PI3K-Akt and NF-κB Pathways in Prostate Cancer |
title_full | Complex Systems Biology Approach in Connecting PI3K-Akt and NF-κB Pathways in Prostate Cancer |
title_fullStr | Complex Systems Biology Approach in Connecting PI3K-Akt and NF-κB Pathways in Prostate Cancer |
title_full_unstemmed | Complex Systems Biology Approach in Connecting PI3K-Akt and NF-κB Pathways in Prostate Cancer |
title_short | Complex Systems Biology Approach in Connecting PI3K-Akt and NF-κB Pathways in Prostate Cancer |
title_sort | complex systems biology approach in connecting pi3k-akt and nf-κb pathways in prostate cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468646/ https://www.ncbi.nlm.nih.gov/pubmed/30813597 http://dx.doi.org/10.3390/cells8030201 |
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