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Damm, S; Koefinger, P; Stefan, M; Wels, C; Mehes, G; Richtig, E; Kerl, H; Otte, M; Schaider, H.
HGF-promoted motility in primary human melanocytes depends on CD44v6 regulated via NF-kappa B, Egr-1, and C/EBP-beta.
J Invest Dermatol. 2010; 130(7): 1893-1903. [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Damm Sabine
Kerl Helmut
Köfinger Petra
Richtig Erika
Schaider Helmut
Wels Christian
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Number of Figures: 10
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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-kappaB dependent because BAY 11-7082, an inhibitor of NF-kappaB activation, but not interference with the mitogen-activated protein kinase or phosphatidylinositol 3-kinase cascade, antagonized HGF-induced CD44v6 expression. NF-kappaB-mediated transcriptional regulation of CD44v6 involves the transcription factors Egr-1 and CCAAT enhancer-binding protein-beta (C/EBP-beta). In gel shift assays, the initial binding of p100/p52 NF-kappaB, C/EBP-beta, and Egr-1 to the CD44 promoter experienced reshuffling toward increased affinity of C/EBP-beta 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-kappaB/C/EBP-beta and Egr-1.
Find related publications in this database (using NLM MeSH Indexing)
Antigens, CD44 - genetics Antigens, CD44 - metabolism
CCAAT-Enhancer-Binding Protein-beta - metabolism
Cell Line, Tumor -
Cell Movement - drug effects Cell Movement - physiology
Early Growth Response Protein 1 - metabolism
Gene Expression Regulation, Neoplastic - physiology
Hepatocyte Growth Factor - metabolism Hepatocyte Growth Factor - pharmacology
Humans -
Immunohistochemistry -
Lymphatic Metastasis -
Melanocytes - metabolism Melanocytes - pathology
Melanoma - metabolism Melanoma - physiopathology Melanoma - secondary
NF-kappa B - metabolism
Nevus - metabolism Nevus - pathology
Signal Transduction - physiology
Skin Neoplasms - metabolism Skin Neoplasms - pathology Skin Neoplasms - physiopathology
Transcription, Genetic - physiology

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