Linked Life Data

19190323

Source:http://linkedlifedata.com/resource/pubmed/id/19190323

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-2-17
pubmed:abstractText
Wnt/beta-catenin signaling plays an essential role in colon carcinogenesis. Galectin-3, a beta-galactoside-binding protein, has been implicated in Wnt signaling, but the precise mechanisms by which galectin-3 modulates the Wnt pathway are unknown. In the present study, we determined the effects of galectin-3 on the Wnt/beta-catenin pathway in colon cancer cells, as well as the mechanisms involved. Galectin-3 levels were manipulated in human colon cancer cells by stable transfection of galectin-3 antisense, short hairpin RNA, or full-length galectin-3 cDNA, and effects on beta-catenin levels, subcellular distribution, and Wnt signaling were determined. Galectin-3 levels correlated with beta-catenin levels in a variety of colon cancer cell lines. Down-regulation of galectin-3 resulted in decreased beta-catenin protein levels but no change in beta-catenin mRNA levels, suggesting that galectin-3 modulates beta-catenin by another mechanism. Reduction of galectin-3 led to reduced nuclear beta-catenin with a concomitant decrease in TCF4 transcriptional activity and expression of its target genes. Conversely, transfection of galectin-3 cDNA into colon cancer cells increased beta-catenin expression and TCF4 transcriptional activity. Down-regulation of galectin-3 resulted in AKT and glycogen synthase kinase-3beta (GSK-3beta) dephosphorylation and increased GSK activity, increasing beta-catenin phosphorylation and degradation. Ly294002, an inhibitor of phosphatidylinositol 3-kinase, and dominant-negative AKT, suppressed TCF4 transcriptional activity induced by galectin-3 whereas LiCl, a GSK-3beta inhibitor, increased TCF4 activity, mimicking the effects of galectin-3. These results suggest that galectin-3 mediates Wnt signaling, at least in part, by regulating GSK-3beta phosphorylation and activity via the phosphatidylinositol 3-kinase/AKT pathway, and, thus, the degradation of beta-catenin in colon cancer cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
69
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1343-9
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:19190323-Adenocarcinoma, pubmed-meshheading:19190323-Cell Line, Tumor, pubmed-meshheading:19190323-Colonic Neoplasms, pubmed-meshheading:19190323-Colorectal Neoplasms, pubmed-meshheading:19190323-Down-Regulation, pubmed-meshheading:19190323-Galectin 3, pubmed-meshheading:19190323-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19190323-Genes, Reporter, pubmed-meshheading:19190323-Glycogen Synthase Kinase 3, pubmed-meshheading:19190323-Humans, pubmed-meshheading:19190323-Immunohistochemistry, pubmed-meshheading:19190323-Luciferases, pubmed-meshheading:19190323-Plasmids, pubmed-meshheading:19190323-Polymerase Chain Reaction, pubmed-meshheading:19190323-RNA, Messenger, pubmed-meshheading:19190323-Signal Transduction, pubmed-meshheading:19190323-Transfection, pubmed-meshheading:19190323-Up-Regulation, pubmed-meshheading:19190323-Wnt Proteins, pubmed-meshheading:19190323-beta Catenin
pubmed:year
2009
pubmed:articleTitle
Galectin-3 mediates nuclear beta-catenin accumulation and Wnt signaling in human colon cancer cells by regulation of glycogen synthase kinase-3beta activity.
pubmed:affiliation
Department of Gastroenterology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural