Dataset Information

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

ABSTRACT: Phosphatidylinositol 3'-OH kinase (PI3K)-Akt and transcription factor NF-?B are important molecules involved in the regulation of cell proliferation, apoptosis, and oncogenesis. Both PI3K-Akt and Nuclear Factor-kappaB (NF-?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-?B pathways was constructed to determine which signaling components contribute to adaptive behavior and coordination. In silico experiments conducted using PI3K-Akt and NF-?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?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.

SUBMITTER: Shankar E

PROVIDER: S-EPMC6468646 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Shankar Eswar E Weis Michael C MC Avva Jayant J Shukla Sanjeev S Shukla Meenakshi M Sreenath Sree N SN Gupta Sanjay S

Cells 20190226 3

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 c ...[more]

PMID: 30813597

Similar Datasets

Project description:Background Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The survival rate of patients with metastatic disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis is not likely to identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic pathways that are jointly supported by both mRNA and protein expression data in two distinct human metastatic OS models. Results mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway analysis of the differentially regulated genes and glycoproteins separately revealed pathways associated to metastasis including cell cycle regulation, immune response, and epithelial-to-mesenchymal-transition. However, no common significant pathway was found at both genomic and proteomic levels between the two metastatic models, suggesting a very different biological nature of the cell lines. To address this issue, we used a topological significance analysis based on a “shortest path” algorithm to identify topological nodes, which uncovered additional biological information with respect to the genomic and glycoproteomic profiles but remained hidden from the direct analyses. Pathway analysis of the significant topological nodes revealed a striking concordance between the models and identified significant common pathways, including “Cytoskeleton remodeling/TGF/WNT”, “Cytoskeleton remodeling/Cytoskeleton remodeling”, and “Cell adhesion/Chemokines and adhesion”. Of these, the “Cytoskeleton remodeling/TGF/WNT” was the top ranked common pathway from the topological analysis of the genomic and proteomic profiles in the two metastatic models. The up-regulation of proteins in the “Cytoskeleton remodeling/TGF/WNT” pathway in the SaOS-2/LM7 and HOS/143B models was further validated using an orthogonal Reverse Phase Protein Array platform. Conclusions In this study, we used a systems biology approach by integrating genomic and proteomic data to identify key and common metastatic mechanisms in OS. The use of the topological analysis revealed hidden biological pathways that are known to play critical roles in metastasis. Wnt signaling has been previously implicated in OS and other tumors, and inhibitors of Wnt signaling pathways are available for clinical testing. Further characterization of this common pathway and other topological pathways identified from this study may lead to a novel therapeutic strategy for the treatment of metastatic OS.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets