Linked Life Data

15375530

Source:http://linkedlifedata.com/resource/pubmed/id/15375530

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-9-17
pubmed:abstractText
Hepatocyte growth factor (HGF), the ligand for the c-met proto-oncogene product, is a multifunctional protein that enhances tumor cell motility, extracellular matrix invasion, and mitogenic or morphogenic activities of various cell types. In this study we examined the expression of the c-Met receptor in human oral squamous cell carcinoma (SCC) in vivo and in vitro to explore its relationship to tumor progression and invasiveness. Biopsy specimens of human oral SCC were immunohistochemically stained for c-Met. Nearly all primary oral SCC lesions and lymph node metastases consistently showed intense staining for c-Met, whereas normal oral mucosa showed faint to negative staining only on basal cells. In a panel of human oral SCC cell lines, we found a strong correlation between the levels of c-Met expression and the cells' response to HGF in motility and invasion assays. Sensitivity to HGF also correlated with the expression of the c-Met 9-kb mRNA. When the non-invasive HOC-605 cell line, which expresses a low level of c-Met receptor, was transfected with an expression plasmid containing human c-met cDNA, the transfectant cells showed motile and invasive responses to HGF. Immunostaining and immunoprecipitation studies demonstrated that E-cadherin and c-Met were physically associated at SCC cell-cell junctions, suggesting a direct role for c-Met in induction of junctional integrity. Importantly, HGF caused a rapid elevation of unbound beta-catenin, suggesting its availability for nuclear signal transduction and triggering of cell motility and invasiveness. Thus, overexpression of c-Met may facilitate disruption of E-cadherin junctions. Collectively, these results suggest that HGF/c-Met signaling is a common event in oral SCC that may trigger phenotype modulation and enhanced invasion and metastasis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
831-40
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15375530-Blotting, Northern, pubmed-meshheading:15375530-Cadherins, pubmed-meshheading:15375530-Carcinoma, Squamous Cell, pubmed-meshheading:15375530-Cell Line, Tumor, pubmed-meshheading:15375530-Cell Movement, pubmed-meshheading:15375530-Cytoskeletal Proteins, pubmed-meshheading:15375530-Epidermal Growth Factor, pubmed-meshheading:15375530-Hepatocyte Growth Factor, pubmed-meshheading:15375530-Humans, pubmed-meshheading:15375530-Immunohistochemistry, pubmed-meshheading:15375530-Intercellular Junctions, pubmed-meshheading:15375530-Mouth Neoplasms, pubmed-meshheading:15375530-Neoplasm Invasiveness, pubmed-meshheading:15375530-Phosphorylation, pubmed-meshheading:15375530-Proto-Oncogene Proteins c-met, pubmed-meshheading:15375530-Signal Transduction, pubmed-meshheading:15375530-Trans-Activators, pubmed-meshheading:15375530-Tyrosine, pubmed-meshheading:15375530-beta Catenin
pubmed:year
2004
pubmed:articleTitle
Overexpression of c-met in oral SCC promotes hepatocyte growth factor-induced disruption of cadherin junctions and invasion.
pubmed:affiliation
Department of Stomatology, University of California San Francisco, San Francisco, CA 94143, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.