Source:http://linkedlifedata.com/resource/pubmed/id/10744074
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
|
pubmed:dateCreated |
2000-4-12
|
pubmed:abstractText |
The cadherin-mediated cell-cell adhesion system plays a critical role in normal development and morphogenesis. Inactivation of this system is thought to be responsible for cancer invasion and metastasis. A human hepatocellular carcinoma (HCC) cell line, KYN-2, was observed to have great potential for intrahepatic metastasis when orthotopically implanted into the liver of SCID mice. In vitro cultures of KYN-2 cells showed that they formed trabecular structures in suspension but lost tight cell-cell adhesion and became scattered when attached to a substratum such as collagen or fibronectin. In response to adhesion to the substratum, subcellular colocalization of E-cadherin and actin filaments were shown to be reduced, and a significant amount of alpha-catenin was dissociated from the E-cadherin-catenin complex in KYN-2 cells. These changes of cell-cell adhesion were blocked by inhibitory monoclonal antibodies against beta1 and beta5 integrins. We found that c-Src was coimmunoprecipitated with E-cadherin-catenin complex and was tyrosine-dephosphorylated and activated in the adherent cells. The tyrosine dephosphorylation of c-Src was induced by cell adhesion to the substratum and inhibited by addition of inhibitory monoclonal antibodies against beta1 and beta5 integrins. These findings indicate that integrin-mediated cell-substratum adhesion inhibits cadherin-mediated cell-cell adhesion, possibly through c-Src activation, and suggest that this cross-talk mediates transient inactivation of the cadherin system and plays an important role in intrahepatic metastasis of human HCC. Modulation of this interaction might provide a new approach to prevent metastasis and recurrence of HCC.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CSK tyrosine-protein kinase,
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Integrins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
|
pubmed:status |
MEDLINE
|
pubmed:month |
Mar
|
pubmed:issn |
0023-6837
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
80
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
387-94
|
pubmed:dateRevised |
2011-11-2
|
pubmed:meshHeading |
pubmed-meshheading:10744074-Cadherins,
pubmed-meshheading:10744074-Carcinoma, Hepatocellular,
pubmed-meshheading:10744074-Cell Adhesion,
pubmed-meshheading:10744074-Cell Communication,
pubmed-meshheading:10744074-Cytoskeletal Proteins,
pubmed-meshheading:10744074-Enzyme Activation,
pubmed-meshheading:10744074-Humans,
pubmed-meshheading:10744074-Integrins,
pubmed-meshheading:10744074-Liver Neoplasms,
pubmed-meshheading:10744074-Neoplasm Metastasis,
pubmed-meshheading:10744074-Protein-Tyrosine Kinases,
pubmed-meshheading:10744074-Trans-Activators,
pubmed-meshheading:10744074-Tumor Cells, Cultured,
pubmed-meshheading:10744074-beta Catenin
|
pubmed:year |
2000
|
pubmed:articleTitle |
Loss of cell-cell contact is induced by integrin-mediated cell-substratum adhesion in highly-motile and highly-metastatic hepatocellular carcinoma cells.
|
pubmed:affiliation |
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|