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...

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Autores principales:	H Billur Engin, Emre Guney, Ozlem Keskin, Baldo Oliva, Attila Gursoy
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/830506bb3c5b454fb76d3a60cd73bd18
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id	oai:doaj.org-article:830506bb3c5b454fb76d3a60cd73bd18
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spelling	oai:doaj.org-article:830506bb3c5b454fb76d3a60cd73bd182021-11-18T08:45:00ZIntegrating structure to protein-protein interaction networks that drive metastasis to brain and lung in breast cancer.1932-620310.1371/journal.pone.0081035https://doaj.org/article/830506bb3c5b454fb76d3a60cd73bd182013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24278371/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Blocking 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.H Billur EnginEmre GuneyOzlem KeskinBaldo OlivaAttila GursoyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e81035 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q H Billur Engin Emre Guney Ozlem Keskin Baldo Oliva Attila Gursoy Integrating structure to protein-protein interaction networks that drive metastasis to brain and lung in breast cancer.
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	article
author	H Billur Engin Emre Guney Ozlem Keskin Baldo Oliva Attila Gursoy
author_facet	H Billur Engin Emre Guney Ozlem Keskin Baldo Oliva Attila Gursoy
author_sort	H Billur Engin
title	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_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_sort	integrating structure to protein-protein interaction networks that drive metastasis to brain and lung in breast cancer.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/830506bb3c5b454fb76d3a60cd73bd18
work_keys_str_mv	AT hbillurengin integratingstructuretoproteinproteininteractionnetworksthatdrivemetastasistobrainandlunginbreastcancer AT emreguney integratingstructuretoproteinproteininteractionnetworksthatdrivemetastasistobrainandlunginbreastcancer AT ozlemkeskin integratingstructuretoproteinproteininteractionnetworksthatdrivemetastasistobrainandlunginbreastcancer AT baldooliva integratingstructuretoproteinproteininteractionnetworksthatdrivemetastasistobrainandlunginbreastcancer AT attilagursoy integratingstructuretoproteinproteininteractionnetworksthatdrivemetastasistobrainandlunginbreastcancer
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Integrating structure to protein-protein interaction networks that drive metastasis to brain and lung in breast cancer.

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