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Issue 8, 2012
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A taxonomy of organ-specific breast cancer metastases based on a proteinprotein interaction network

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Abstract

We carried out a systems-level study of the mechanisms underlying organ-specific metastases of breast cancer. We followed a network-based approach using microarray expression data from human breast cancer metastases to select organ-specific proteins that exert a range of functions allowing cell survival and growth in the microenvironment of distant organs. MinerProt, a home-made software application, was used to group organ-specific signatures of brain (1191 genes), bone (1623 genes), liver (977 genes) and lung (254 genes) metastases by function and select the most differentially expressed gene in each function. As a result, we obtained 19 functional representative proteins in brain, 23 in bone, 15 in liver and 9 in lung, with which we constructed four organ-specific proteinprotein interaction networks. The network taxonomy included seven proteins that interacted in brain metastasis, which were mainly associated with signal transduction. Proteins related to immune response functions were bone specific, while those involved in proteolysis, signal transduction and hepatic glucose metabolism were found in liver metastasis. No experimental proteinprotein interaction was found in lung metastasis; thus, computationally determined interactions were included in this network. Moreover, three of these selected genes (CXCL12, DSC2 and TFDP2) were associated with progression to specific organs when tested in an independent dataset. In conclusion, we present a network-based approach to filter information by selecting key protein functions as metastatic markers or therapeutic targets.

Graphical abstract: A taxonomy of organ-specific breast cancer metastases based on a protein–protein interaction network

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Publication details

The article was received on 15 Nov 2011, accepted on 27 Apr 2012 and first published on 07 May 2012


Article type: Paper
DOI: 10.1039/C2MB25104C
Citation: Mol. BioSyst., 2012,8, 2085-2096
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    A taxonomy of organ-specific breast cancer metastases based on a proteinprotein interaction network

    R. Sanz-Pamplona, J. García-García, S. Franco, X. Messeguer, K. Driouch, B. Oliva and À. Sierra, Mol. BioSyst., 2012, 8, 2085
    DOI: 10.1039/C2MB25104C

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