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Issue 9, 2012
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Cancer develops, progresses and responds to therapies through restricted perturbation of the proteinprotein interaction network

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Abstract

The products of genes mutated or differentially expressed in cancer tend to occupy central positions within the network of proteinprotein 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.

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

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Publication details

The article was received on 08 Mar 2012, accepted on 02 Jul 2012 and first published on 04 Jul 2012


Article type: Paper
DOI: 10.1039/C2IB20052J
Citation: Integr. Biol., 2012,4, 1038-1048
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    Cancer develops, progresses and responds to therapies through restricted perturbation of the proteinprotein interaction network

    J. Serra-Musach, H. Aguilar, F. Iorio, F. Comellas, A. Berenguer, J. Brunet, J. Saez-Rodriguez and M. A. Pujana, Integr. Biol., 2012, 4, 1038
    DOI: 10.1039/C2IB20052J

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