Linked Life Data

18922979

Source:http://linkedlifedata.com/resource/pubmed/id/18922979

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2008-10-16
pubmed:abstractText
Overexpression of focal adhesion kinase (FAK) has been well correlated with tumor development and/or the maintenance of tumor phenotype. In addition, inappropriate activation of the extracellular regulated kinase (ERK) signaling pathway is common to many human cancers. In the present study, we investigated the interplay between FAK and ERK in androgen-independent prostate cancer cells (PC3 and DU145 cells). We observed that suppression of FAK expression using small interfering RNA-mediated knockdown decreased the clonogenic activity, whereas overexpression of FAK increased it. We also observed that detachment of PC3 and DU145 cells from their substrate induced tyrosine phosphorylation of FAK. ERK knockdown diminished FAK protein levels and tyrosine phosphorylation of FAK as well as FAK promoter-reporter activity. We also tested the effect of MEK inhibitors and small interfering RNA-mediated knockdown of ERK1 and/or ERK2 on cell proliferation, invasiveness, and growth in soft agar of PC3 and DU145 cells. Inhibition of ERK signaling grossly impaired clonogenicity as well as invasion through Matrigel. However, inhibition of ERK signaling resulted in only a modest inhibition of 3H-thymidine incorporation and no effect on overall viability of the cells or increased sensitivity to anoikis. Taken together, these data show, for the first time, a requirement for FAK in aggressive phenotype of prostate cancer cells; reveal interdependence of FAK and ERK1/2 for clonogenic and invasive activity of androgen-independent prostate cancer cells; suggest a role for ERK regulation of FAK in substrate-dependent survival; and show for the first time, in any cell type, the regulation of FAK expression by ERK signaling pathway.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1541-7786
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1639-48
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18922979-Androgens, pubmed-meshheading:18922979-Anoikis, pubmed-meshheading:18922979-Cell Line, Tumor, pubmed-meshheading:18922979-Cell Proliferation, pubmed-meshheading:18922979-Cell Survival, pubmed-meshheading:18922979-Enzyme Activation, pubmed-meshheading:18922979-Focal Adhesion Protein-Tyrosine Kinases, pubmed-meshheading:18922979-Humans, pubmed-meshheading:18922979-MAP Kinase Signaling System, pubmed-meshheading:18922979-Male, pubmed-meshheading:18922979-Matrix Metalloproteinase 9, pubmed-meshheading:18922979-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:18922979-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:18922979-Neoplasm Invasiveness, pubmed-meshheading:18922979-Phenotype, pubmed-meshheading:18922979-Phosphorylation, pubmed-meshheading:18922979-Prostatic Neoplasms, pubmed-meshheading:18922979-RNA, Small Interfering, pubmed-meshheading:18922979-Tumor Stem Cell Assay
pubmed:year
2008
pubmed:articleTitle
Focal adhesion kinase controls aggressive phenotype of androgen-independent prostate cancer.
pubmed:affiliation
Program in Urosciences, Division of Urology-Department of Surgery, University of Colorado Denver School of Medicine, Denver, Colorado, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural