FGF Receptor and Wnt-1 Signaling Cooperate in Mammary Tumorigenesis
Transcriptomics Dataset
FAIR Metrics
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General Information
AccessionGSE17916
TitleFGF Receptor and Wnt-1 Signaling Cooperate in Mammary Tumorigenesis
DescriptionThe fibroblast growth factor pathway is known to cooperate with the highly oncogenic Wnt/beta-catenin pathway in mouse models of breast cancer. To investigate the mechanisms involved in this cooperativity, we utilized MMTV-driven transgenic mouse lines expressing a drug-inducible model for FGF Receptor signaling (iFGFR) crossed with the previously characterized MMTV-Wnt-1 mouse model. In these bigenic mice, both iFGFR1 and iFGFR2 activation resulted in a dramatic enhancement of mammary tumorigenesis. Tumor microarray analysis identified no transcriptional enhancement of Wnt/beta-catenin targets, however, identified a protein translational gene signature that also correlated with elevated FGFR1 and FGFR2 expression in several human breast cancer data sets. Additionally, iFGFR1 activation resulted in enhanced polysome recruitment and a marked increase in protein expression of several different Wnt/beta-catenin target oncogenes. Rapid FGFR-induced ERK activation and phosphorylation of key translation regulators was observed both in vivo in the transgenic mouse model, and in human breast cancer cell lines treated with exogenous FGF. These studies suggest that translational regulation is a key rate-limiting step required for oncogenic cooperativity between the Wnt and FGF pathways.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17916
RepositoryGene Expression Omnibus
Tools used to analyze the dataset

Keyword
Dataset Accession

Enrichr
Published May 2016
A comprehensive gene set enrichment analysis web server 2016 update
7759
65
Characteristic Direction
Published March 2014
A geometrical multivariate approach to identify differentially expressed genes
26829
GeneMANIA
Published June 2010
Biological network integration for gene prioritization and predicting gene function
7435
L1000CDS2
Published August 2016
An ultra-fast LINCS L1000 Characteristic Direction signature search engine
7756
PAEA
Published November 2015
Enrichment analysis tool implementing the principal angle method
3879
Canned Analyses generated with the dataset

Dataset Accession
Tool Name
Direction
Cell Type
Hs Gene Symbol
Mm Gene Symbol
Geneset

Small molecules which mimic FGFR1 activemutant
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse FGFR1 activemutant
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic FGFR2 activemutant
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse FGFR2 activemutant
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in FGFR1 activemutant
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Enrichment analysis of genes dysregulated in FGFR2 activemutant
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Interaction network and enrichment analysis of genes downregulated in FGFR1 activemutant
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in FGFR1 activemutant
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes downregulated in FGFR2 activemutant
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in FGFR2 activemutant
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
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