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Cancer develops, progresses and responds to therapies through restricted perturbation of the protein–protein interaction network

The products of genes mutated or differentially expressed in cancer tend to occupy central positions within the network of protein–protein interactions, or the interactome network. Integration of different types of gene and protein relationships has considerably increased the understanding of the me...

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Autores principales: Serra-Musach, Jordi, Aguilar, Helena, Iorio, Francesco, Comellas, Francesc, Berenguer, Antoni, Brunet, Joan, Saez-Rodriguez, Julio, Pujana, Miguel Angel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699251/
https://www.ncbi.nlm.nih.gov/pubmed/22806580
http://dx.doi.org/10.1039/c2ib20052j
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author Serra-Musach, Jordi
Aguilar, Helena
Iorio, Francesco
Comellas, Francesc
Berenguer, Antoni
Brunet, Joan
Saez-Rodriguez, Julio
Pujana, Miguel Angel
author_facet Serra-Musach, Jordi
Aguilar, Helena
Iorio, Francesco
Comellas, Francesc
Berenguer, Antoni
Brunet, Joan
Saez-Rodriguez, Julio
Pujana, Miguel Angel
author_sort Serra-Musach, Jordi
collection PubMed
description The products of genes mutated or differentially expressed in cancer tend to occupy central positions within the network of protein–protein interactions, or the interactome network. Integration of different types of gene and protein relationships has considerably increased the understanding of the mechanisms of carcinogenesis, while also enhancing the applicability of expression signatures. In this scenario, however, it remains unknown how cancer develops, progresses and responds to therapies in a potentially controlled manner at the systems level. Here, by applying the concepts of load transfer and cascading failures in power grids, we examine the impact and transmission of cancer-related gene expression changes in the interactome network. Relative to random perturbations, this study reveals topological robustness associated with all cancer conditions. In addition, experimental perturbation of a central cancer node, which consists of over-expression of the α-synuclein (SNCA) protein in MCF7 breast cancer cells, also reveals robustness. Conversely, a search for proteins with an opposite topological impact identifies the autophagy pathway. Mechanistically, the existence of smaller shortest paths among cancer-related proteins appears to be a topological feature that partially contributes to the restricted perturbation of the network. Together, the results of this study suggest that cancer develops, progresses and responds to therapies following controlled, restricted perturbation of the interactome network.
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spelling pubmed-46992512016-01-15 Cancer develops, progresses and responds to therapies through restricted perturbation of the protein–protein interaction network Serra-Musach, Jordi Aguilar, Helena Iorio, Francesco Comellas, Francesc Berenguer, Antoni Brunet, Joan Saez-Rodriguez, Julio Pujana, Miguel Angel Integr Biol (Camb) Chemistry The products of genes mutated or differentially expressed in cancer tend to occupy central positions within the network of protein–protein interactions, or the interactome network. Integration of different types of gene and protein relationships has considerably increased the understanding of the mechanisms of carcinogenesis, while also enhancing the applicability of expression signatures. In this scenario, however, it remains unknown how cancer develops, progresses and responds to therapies in a potentially controlled manner at the systems level. Here, by applying the concepts of load transfer and cascading failures in power grids, we examine the impact and transmission of cancer-related gene expression changes in the interactome network. Relative to random perturbations, this study reveals topological robustness associated with all cancer conditions. In addition, experimental perturbation of a central cancer node, which consists of over-expression of the α-synuclein (SNCA) protein in MCF7 breast cancer cells, also reveals robustness. Conversely, a search for proteins with an opposite topological impact identifies the autophagy pathway. Mechanistically, the existence of smaller shortest paths among cancer-related proteins appears to be a topological feature that partially contributes to the restricted perturbation of the network. Together, the results of this study suggest that cancer develops, progresses and responds to therapies following controlled, restricted perturbation of the interactome network. Royal Society of Chemistry 2012-08-21 2012-07-18 /pmc/articles/PMC4699251/ /pubmed/22806580 http://dx.doi.org/10.1039/c2ib20052j Text en This journal is © The Royal Society of Chemistry 2012 http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Chemistry
Serra-Musach, Jordi
Aguilar, Helena
Iorio, Francesco
Comellas, Francesc
Berenguer, Antoni
Brunet, Joan
Saez-Rodriguez, Julio
Pujana, Miguel Angel
Cancer develops, progresses and responds to therapies through restricted perturbation of the protein–protein interaction network
title Cancer develops, progresses and responds to therapies through restricted perturbation of the protein–protein interaction network
title_full Cancer develops, progresses and responds to therapies through restricted perturbation of the protein–protein interaction network
title_fullStr Cancer develops, progresses and responds to therapies through restricted perturbation of the protein–protein interaction network
title_full_unstemmed Cancer develops, progresses and responds to therapies through restricted perturbation of the protein–protein interaction network
title_short Cancer develops, progresses and responds to therapies through restricted perturbation of the protein–protein interaction network
title_sort cancer develops, progresses and responds to therapies through restricted perturbation of the protein–protein interaction network
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699251/
https://www.ncbi.nlm.nih.gov/pubmed/22806580
http://dx.doi.org/10.1039/c2ib20052j
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