Integrating structure to protein-protein interaction networks that drive metastasis to brain and lung in breast cancer

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• dc.contributor.author Engin, H Billurca
• dc.contributor.author Güney, Emre, 1983-ca
• dc.contributor.author Keskin, Ozlemca
• dc.contributor.author Oliva Miguel, Baldomeroca
• dc.contributor.author Gursoy, Attilaca
• dc.date.accessioned 2015-05-21T10:57:44Z
• dc.date.available 2015-05-21T10:57:44Z
• dc.date.issued 2013ca
• dc.description.abstract Blocking specific protein interactions can lead to human diseases. Accordingly, protein interactions and the structural knowledge on interacting surfaces of proteins (interfaces) have an important role in predicting the genotype-phenotype relationship. We have built the phenotype specific sub-networks of protein-protein interactions (PPIs) involving the relevant genes responsible for lung and brain metastasis from primary tumor in breast cancer. First, we selected the PPIs most relevant to metastasis causing genes (seed genes), by using the “guilt-by-association” principle. Then, we modeled structures of the interactions whose complex forms are not available in Protein Databank (PDB). Finally, we mapped mutations to interface structures (real and modeled), in order to spot the interactions that might be manipulated by these mutations. Functional analyses performed on these sub-networks revealed the potential relationship between immune system-infectious diseases and lung metastasis progression, but this connection was not observed significantly in the brain metastasis. Besides, structural analyses showed that some PPI interfaces in both metastasis sub-networks are originating from microbial proteins, which in turn were mostly related with cell adhesion. Cell adhesion is a key mechanism in metastasis, therefore these PPIs may be involved in similar molecular pathways that are shared by infectious disease and metastasis. Finally, by mapping the mutations and amino acid variations on the interface regions of the proteins in the metastasis sub-networks we found evidence for some mutations to be involved in the mechanisms differentiating the type of the metastasis.en
• dc.description.sponsorship This work is supported by Spanish Government (MINECO) grant FEDER BIO2011-22568 and EUI2009-04018 (ERASysBio + SHIPREC) and The Scientific and Technological Research Council of Turkey (TUBITAK) grant 113E164.en
• dc.format.mimetype application/pdfca
• dc.identifier.citation Billur Engin H, Guney E, Keskin O, Oliva B, Gursoy A. Integrating structure to protein-protein interaction networks that drive metastasis to brain and lung in breast cancer. PLoS ONE. 2013;8(11):e81035. DOI: 10.1371/journal.pone.0081035ca
• dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0081035
• dc.identifier.issn 1932-6203ca
• dc.identifier.uri http://hdl.handle.net/10230/23604
• dc.language.iso engca
• dc.publisher Public Library of Science (PLoS)ca
• dc.relation.ispartof PLoS ONE. 2013;8(11):e81035
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2011-22568
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/EUI2009-04018
• dc.rights © 2013 Engin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are crediteden
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.subject.other Mama -- Càncer -- Aspectes genèticsca
• dc.subject.other Proteïnes -- Metabolismeca
• dc.title Integrating structure to protein-protein interaction networks that drive metastasis to brain and lung in breast canceren
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca