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Title: Rewiring of human lung cell lineage and mitotic networks in lung adenocarcinomas      
dateReleased:
04-01-2013
description:
Naturally occurring genetic polymorphisms influence patterns of gene expression in normal tissues, and can provide a molecular view of the component cell lineages and signaling pathways responsible for normal tissue architecture. Analysis of the coordinated changes in this architecture that take place during tumor development can help to identify the functional roles of oncogenes or tumor suppressors and provide potential new therapeutic targets. We have applied a network analysis approach to a set of 92 normal human lung samples from cancer patients and their matched adenocarcinomas. We have identified networks associated with particular cell lineages (alveolar type 2 pneumocytes and Clara cells) in normal lung and document the changes in these networks that accompany transformation to adenocarcinomas. Expression of the transcription factor NKX2-1 (TTF1) is linked to surfactant protein markers of the alveolar type 2 lineage in normal and transformed lung cells, but its network is rewired in tumors to include pathways linked to cell growth such as glutaminase (GLS2). Analysis of mitotic networks revealed the presence of novel components such as the kinase VRK1 that are preferentially linked to the mitotic cycle in tumors but not in normal lung. We show that shRNA-mediated inhibition of VRK1 cooperates with inhibition of PARP signaling to inhibit growth of lung tumor cells. Targeting of genes that are recruited into tumor mitotic networks may provide a wider therapeutic window than that seen by inhibition of integral components of the mitotic machinery such as Aurora kinases. 87 lung adenocarcinomas and 92 adjacent uninvolved lung tissue samples, 85 matched pairs
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-32665
refinement:
raw
alternateIdentifiers:
32665
keywords:
functional genomics
dateModified:
06-02-2014
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-MEXP-930
name:
Illumina Human-6 v2 Expression BeadChip
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-32665/E-GEOD-32665.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-32665/E-GEOD-32665.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32665
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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