Cargando…
Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer
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-networ...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3838352/ https://www.ncbi.nlm.nih.gov/pubmed/24278371 http://dx.doi.org/10.1371/journal.pone.0081035 |
_version_ | 1782478344433958912 |
---|---|
author | Engin, H. Billur Guney, Emre Keskin, Ozlem Oliva, Baldo Gursoy, Attila |
author_facet | Engin, H. Billur Guney, Emre Keskin, Ozlem Oliva, Baldo Gursoy, Attila |
author_sort | Engin, H. Billur |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3838352 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38383522013-11-25 Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer Engin, H. Billur Guney, Emre Keskin, Ozlem Oliva, Baldo Gursoy, Attila PLoS One Research Article 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. Public Library of Science 2013-11-22 /pmc/articles/PMC3838352/ /pubmed/24278371 http://dx.doi.org/10.1371/journal.pone.0081035 Text en © 2013 Engin et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Engin, H. Billur Guney, Emre Keskin, Ozlem Oliva, Baldo Gursoy, Attila Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer |
title | Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer |
title_full | Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer |
title_fullStr | Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer |
title_full_unstemmed | Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer |
title_short | Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer |
title_sort | integrating structure to protein-protein interaction networks that drive metastasis to brain and lung in breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3838352/ https://www.ncbi.nlm.nih.gov/pubmed/24278371 http://dx.doi.org/10.1371/journal.pone.0081035 |
work_keys_str_mv | AT enginhbillur integratingstructuretoproteinproteininteractionnetworksthatdrivemetastasistobrainandlunginbreastcancer AT guneyemre integratingstructuretoproteinproteininteractionnetworksthatdrivemetastasistobrainandlunginbreastcancer AT keskinozlem integratingstructuretoproteinproteininteractionnetworksthatdrivemetastasistobrainandlunginbreastcancer AT olivabaldo integratingstructuretoproteinproteininteractionnetworksthatdrivemetastasistobrainandlunginbreastcancer AT gursoyattila integratingstructuretoproteinproteininteractionnetworksthatdrivemetastasistobrainandlunginbreastcancer |