Linked Life Data

20023695

Source:http://linkedlifedata.com/resource/pubmed/id/20023695

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2010-3-11
pubmed:abstractText
The Ras oncogene is known to activate three major MAPK pathways, ERK, JNK, p38 and exert distinct cellular phenotypes, that is, apoptosis and invasion through the Ras-MKK3-p38-signaling cascade. We attempted to identify the molecular targets of this pathway that selectively govern the invasive phenotype. Stable transfection of NIH3T3 fibroblasts with MKK3(act) cDNA construct revealed similar p38-dependent in vitro characteristics observed in Ha-Ras(EJ)-transformed NIH3T3 cells, including enhanced invasiveness and anchorage-independent growth correlating with p38 phosphorylation status. To identify the consensus downstream targets of the Ras-MKK3-p38 cascade involved in invasion, in vitro invasion assays were used to isolate highly invasive cells from both, MKK3 and Ha-Ras(EJ) transgenic cell lines. Subsequently a genome-wide transcriptome analysis was employed to investigate differentially regulated genes in invasive Ha-Ras(EJ)- and MKK3(act)-transfected NIH3T3 fibroblasts. Using this phenotype-assisted approach combined with system level protein-interaction network analysis, we identified FOXM1, PLK1 and CDK1 to be differentially regulated in invasive Ha-Ras(EJ)-NIH3T3 and MKK3(act)-NIH3T3 cells. Finally, a FOXM1 RNA-knockdown approach revealed its requirement for both invasion and anchorage-independent growth of Ha-Ras(EJ)- and MKK3(act)-NIH3T3 cells. Together, we identified FOXM1 as a key downstream target of Ras and MKK3-induced cellular in vitro invasion and anchorage-independent growth signaling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1519-30
pubmed:meshHeading
pubmed-meshheading:20023695-Animals, pubmed-meshheading:20023695-Blotting, Western, pubmed-meshheading:20023695-Cell Adhesion, pubmed-meshheading:20023695-Cell Movement, pubmed-meshheading:20023695-Flavonoids, pubmed-meshheading:20023695-Forkhead Transcription Factors, pubmed-meshheading:20023695-Gene Expression Profiling, pubmed-meshheading:20023695-Imidazoles, pubmed-meshheading:20023695-MAP Kinase Kinase 3, pubmed-meshheading:20023695-Mice, pubmed-meshheading:20023695-NIH 3T3 Cells, pubmed-meshheading:20023695-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:20023695-Pyridines, pubmed-meshheading:20023695-RNA Interference, pubmed-meshheading:20023695-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20023695-p38 Mitogen-Activated Protein Kinases, pubmed-meshheading:20023695-ras Proteins
pubmed:year
2010
pubmed:articleTitle
Phenotype-assisted transcriptome analysis identifies FOXM1 downstream from Ras-MKK3-p38 to regulate in vitro cellular invasion.
pubmed:affiliation
Cancer Vaccine, Ludwig Institute for Cancer Research Ltd, Melbourne Centre for Clinical Sciences, Heidelberg, VIC, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't