HGF-promoted motility in primary human melanocytes depends on CD44v6 regulated via NF-kappa B, Egr-1, and C/EBP-beta

Damm, Sabine, Koefinger, Petra, Stefan, Martina, Wels, Christian, Mehes, Gabor, Richtig, Erika, Kerl, Helmut, Otte, Marcus and Schaider, Helmut (2010) HGF-promoted motility in primary human melanocytes depends on CD44v6 regulated via NF-kappa B, Egr-1, and C/EBP-beta. Journal of Investigative Dermatology, 130 7: 1893-1903. doi:10.1038/jid.2010.45


Author Damm, Sabine
Koefinger, Petra
Stefan, Martina
Wels, Christian
Mehes, Gabor
Richtig, Erika
Kerl, Helmut
Otte, Marcus
Schaider, Helmut
Title HGF-promoted motility in primary human melanocytes depends on CD44v6 regulated via NF-kappa B, Egr-1, and C/EBP-beta
Journal name Journal of Investigative Dermatology   Check publisher's open access policy
ISSN 0022-202X
1523-1747
Publication date 2010-01-01
Sub-type Article (original research)
DOI 10.1038/jid.2010.45
Volume 130
Issue 7
Start page 1893
End page 1903
Total pages 11
Place of publication London, United Kingdom
Publisher Nature Publishing
Language eng
Abstract The regulation of CD44v6, a variant of the CD44 family of glycosylated adhesion molecules, through hepatocyte growth factor (HGF) has implications for motility in primary human melanocytes. We show that exposure of primary human melanocytes to HGF results in an increase of CD44v6 expression. Immunostaining of melanocytic lesions revealed low cytoplasmic positivity of CD44v6 in some nevi but high membranous expression in primary cutaneous melanomas, and cutaneous and lymph node metastases. HGF-dependent CD44v6 regulation in melanocytes is NF-B dependent because BAY 11-7082, an inhibitor of NF-B activation, but not interference with the mitogen-activated protein kinase or phosphatidylinositol 3-kinase cascade, antagonized HGF-induced CD44v6 expression. NF-B-mediated transcriptional regulation of CD44v6 involves the transcription factors Egr-1 and CCAAT enhancer-binding protein-Β (C/EBP-Β). In gel shift assays, the initial binding of p100/p52 NF-B, C/EBP-Β, and Egr-1 to the CD44 promoter experienced reshuffling toward increased affinity of C/EBP-Β after HGF stimulation. A blocking antibody to CD44v6 decreased HGF-induced c-Met phosphorylation as well as enhanced random-and site-directed migration. Our data show that HGF-induced motility in primary human melanocytes depends on c-Met-CD44v6 interaction, and that HGF-enhanced CD44v6 expression is required for motility and transcriptional upregulation of CD44v6, presumably mediated through a complex comprising NF-B/C/EBP-Β and Egr-1.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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