Linked Life Data

21750175

Source:http://linkedlifedata.com/resource/pubmed/id/21750175

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2011-7-18
pubmed:abstractText
In this study, we have showed that GCNT2, a gene-encoding glucosaminyl (N-acetyl) transferase 2, I-branching enzyme, is overexpressed in highly metastatic breast cancer cell lines of human and mouse origin and basal-like breast tumor samples. GCNT2 expression is also significantly correlated to the metastatic phenotype in breast tumor samples. Functional studies showed that ectopic expression of GCNT2 enhances cell detachment, adhesion to endothelial cells, cell migration and invasion in vitro, and lung metastasis of breast cancer cells in vivo. Knockdown of GCNT2 expression decreases cell migration and invasion in vitro and lung metastasis in vivo. We have further shown the involvement of GCNT2 in the epithelial-to-mesenchymal transition (EMT). Specifically, the expression of E-cadherin is significantly changed upon GCNT2 expression at the protein level but not at the RNA level. Moreover, we have shown that GCNT2 is a direct target of the TGF-?-smad pathway and that change in GCNT2 expression modulates EMT induced by TGF-?1 treatment. Finally, we have shown that diminution of the glycosyltransferase activity of I-branching ?-1, 6-N-acetylglucosaminyl transferase 2 (GCNT2) abrogates its cell migration and invasion-promoting function and synergistic effect with TGF-? to induce EMT. Our study for the first time showed that GCNT2 is a novel gene contributing to breast cancer metastasis with preferential expression in basal-like breast cancer. Moreover, we discovered that involvement of GCNT2 in EMT and TGF-? signaling, and further glycosylation modification of E-cadherin by GCNT2, are the underlying integrative mechanisms for breast cancer metastasis, implying that blocking TGF-?/GCNT2 signaling is a promising approach for targeting metastatic breast cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1538-7445
pubmed:author
pubmed:copyrightInfo
©2011 AACR.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4846-56
pubmed:meshHeading
pubmed-meshheading:21750175-Animals, pubmed-meshheading:21750175-Breast Neoplasms, pubmed-meshheading:21750175-Cadherins, pubmed-meshheading:21750175-Cell Line, Tumor, pubmed-meshheading:21750175-Cell Movement, pubmed-meshheading:21750175-Dogs, pubmed-meshheading:21750175-Epithelial-Mesenchymal Transition, pubmed-meshheading:21750175-Female, pubmed-meshheading:21750175-Gene Knockdown Techniques, pubmed-meshheading:21750175-Humans, pubmed-meshheading:21750175-Immunohistochemistry, pubmed-meshheading:21750175-Lung Neoplasms, pubmed-meshheading:21750175-Mammary Neoplasms, Experimental, pubmed-meshheading:21750175-Mice, pubmed-meshheading:21750175-Mice, Inbred BALB C, pubmed-meshheading:21750175-Mice, Nude, pubmed-meshheading:21750175-N-Acetylglucosaminyltransferases, pubmed-meshheading:21750175-Neoplasm Invasiveness, pubmed-meshheading:21750175-Neoplasm Metastasis, pubmed-meshheading:21750175-Signal Transduction, pubmed-meshheading:21750175-Transforming Growth Factor beta1
pubmed:year
2011
pubmed:articleTitle
Engagement of I-branching {beta}-1, 6-N-acetylglucosaminyltransferase 2 in breast cancer metastasis and TGF-{beta} signaling.
pubmed:affiliation
The Breast Cancer Biology Program, Barbara Ann Karmanos Cancer Institute; Department of Oncology and Pathology, Wayne State University School of Medicine, HWCRC, Room 840.2, 4100 John R Street, Detroit, MI 48201, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural