Linked Life Data

19567915

Source:http://linkedlifedata.com/resource/pubmed/id/19567915

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
77
pubmed:dateCreated
2009-7-1
pubmed:abstractText
Disruption of intercellular adhesions, increased abundance of alpha(5)beta(1) integrin, and activation of protein kinase Cepsilon (PKCepsilon) correlate with invasion and unfavorable prognosis in lung cancer. However, it remains elusive how these distinct factors contribute to the invasive behavior of cancer cells. Persistent cell motility requires the formation of stable lamellae at the leading edge of a migrating cell. Here, we report that the tight junction protein zonula occludens-1 (ZO-1) preferentially interacts with alpha(5)beta(1) integrin at the lamellae of migrating cells. Disruption of ZO-1 binding to an internal PDZ-binding motif in the alpha(5) cytoplasmic tail prevented the polarized localization of ZO-1 and alpha(5) at the leading edge. Furthermore, silencing of alpha(5) integrin inhibited migration and invasion of lung cancer cells, and silencing of ZO-1 resulted in increased Rac activity and reduced directional cell motility. The formation of the alpha(5)-ZO-1 complex was dependent on PKCepsilon: Phosphorylation of ZO-1 at serine-168 regulated the subcellular localization of ZO-1 and thus controlled its association with alpha(5) integrin. In conclusion, PKCepsilon activation drives the formation of a spatially restricted, promigratory alpha(5)-ZO-1 complex at the leading edge of lung cancer cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1937-9145
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
ra32
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
PKCepsilon regulation of an alpha5 integrin-ZO-1 complex controls lamellae formation in migrating cancer cells.
pubmed:affiliation
Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, FIN-20520 Turku, Finland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't