Linked Life Data

20501702

Source:http://linkedlifedata.com/resource/pubmed/id/20501702

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 12
pubmed:dateCreated
2010-6-3
pubmed:abstractText
Hyperactivation of beta-catenin-T-cell-factor (TCF)-regulated gene transcription is a hallmark of colorectal cancer (CRC). The cell-neural adhesion molecule L1CAM (hereafter referred to as L1) is a target of beta-catenin-TCF, exclusively expressed at the CRC invasive front in humans. L1 overexpression in CRC cells increases cell growth and motility, and promotes liver metastasis. Genes induced by L1 are also expressed in human CRC tissue but the mechanisms by which L1 confers metastasis are still unknown. We found that signaling by the nuclear factor kappaB (NF-kappaB) is essential, because inhibition of signaling by the inhibitor of kappaB super repressor (IkappaB-SR) blocked L1-mediated metastasis. Overexpression of the NF-kappaB p65 subunit was sufficient to increase CRC cell proliferation, motility and metastasis. Binding of the L1 cytodomain to ezrin - a cytoskeleton-crosslinking protein - is necessary for metastasis because when binding to L1 was interrupted or ezrin gene expression was suppressed with specific shRNA, metastasis did not occur. L1 and ezrin bound to and mediated the phosphorylation of IkappaB. We also observed a complex containing IkappaB, L1 and ezrin in the juxtamembrane region of CRC cells. Furthermore, we found that L1, ezrin and phosphorylated p65 are co-expressed at the invasive front in human CRC tissue, indicating that L1-mediated activation of NF-kappaB signaling involving ezrin is a major route of CRC progression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1477-9137
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
123
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2135-43
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Nuclear factor-kappaB signaling and ezrin are essential for L1-mediated metastasis of colon cancer cells.
pubmed:affiliation
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't