Source:http://linkedlifedata.com/resource/pubmed/id/17804733
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
17
|
| pubmed:dateCreated |
2007-9-6
|
| pubmed:abstractText |
Recently, we described phorbol ester-induced expression of the brain and skin serine proteinase Bssp/kallikrein 6 (Klk6), the mouse orthologue of human KLK6, in mouse back skin and in advanced tumor stages of a well-established multistage tumor model. Here, we show KLK6 up-regulation in squamous skin tumors of human patients and in tumors of other epithelial tissues. Ectopic Klk6 expression in mouse keratinocyte cell lines induces a spindle-like morphology associated with accelerated proliferation, migration, and invasion capacity. We found reduced E-cadherin protein levels in the cell membrane and nuclear translocation of beta-catenin in Klk6-expressing mouse keratinocytes and human HEK293 cells transfected with a KLK6 expression plasmid. Additionally, HEK293 cells exhibited induced T-cell factor-dependent transcription and impaired cell-cell adhesion in the presence of KLK6, which was accompanied by induced E-cadherin ectodomain shedding. Interestingly, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-3 interfere with KLK6-induced E-cadherin ectodomain shedding and rescue the cell-cell adhesion defect in vitro, suggesting the involvement of matrix metalloproteinase and/or a disintegrin and metalloproteinase (ADAM) proteolytic activity. In line with this assumption, we found increased levels of the mature 62-kDa ADAM10 proteinase in cells expressing ectopic KLK6 compared with mock controls. Finally, enhanced epidermal keratinocyte proliferation and migration in concert with decreased E-cadherin protein levels are confirmed in an in vivo Klk6 transgenic mouse model.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/KLK6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Kallikreins,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinases,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0008-5472
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
67
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
8198-206
|
| pubmed:meshHeading |
pubmed-meshheading:17804733-Animals,
pubmed-meshheading:17804733-Cadherins,
pubmed-meshheading:17804733-Carcinoma, Squamous Cell,
pubmed-meshheading:17804733-Cell Adhesion,
pubmed-meshheading:17804733-Cell Communication,
pubmed-meshheading:17804733-Cell Movement,
pubmed-meshheading:17804733-Cell Proliferation,
pubmed-meshheading:17804733-Cells, Cultured,
pubmed-meshheading:17804733-Chick Embryo,
pubmed-meshheading:17804733-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17804733-Humans,
pubmed-meshheading:17804733-Kallikreins,
pubmed-meshheading:17804733-Keratinocytes,
pubmed-meshheading:17804733-Matrix Metalloproteinases,
pubmed-meshheading:17804733-Mice,
pubmed-meshheading:17804733-Mice, Transgenic,
pubmed-meshheading:17804733-Precancerous Conditions,
pubmed-meshheading:17804733-Protein Structure, Tertiary,
pubmed-meshheading:17804733-Skin Neoplasms,
pubmed-meshheading:17804733-Transfection,
pubmed-meshheading:17804733-beta Catenin
|
| pubmed:year |
2007
|
| pubmed:articleTitle |
Kallikrein 6 induces E-cadherin shedding and promotes cell proliferation, migration, and invasion.
|
| pubmed:affiliation |
Division of Signal Transduction and Growth Control, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|