Met and hepatocyte growth factor/scatter factor signal transduction in normal melanocytes and melanoma cells

Ruth Halaban, Jeffrey S. Rubin, Yoko Funasaka, Melanie Cobb, Teri Boulton, Donna Faletto, Eliot Rosen, Andrew Chan, Karen Yoko, Wain White, Christopher Cook, Gisela Moellmann

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162 Scopus citations

Abstract

The proto-oncogene c-MET encodes a transmembrane tyrosine kinase receptor for hepatocyte growth factor/ scatter factor (HGF/SF). HGF/SF stimulates the proliferation and motility of various cell types. Because HGF/SF is also a melanocyte mitogen, we investigated the biological role of HGF/SF, including c-Met expression, activation and signal transduction, in normal and malignant human melanocytes. We show that HGF/SF is mitogenic in the presence of synergistic factors, such as basic fibroblast growth factor (bFGF) and mast cell growth factor (MGF) and that, by itself, it stimulates the motility of normal human melanocytes. The ligand also maintained high levels of tyrosinase activity and melanin content in theses cells. Signal transduction by HGF/SF included phosphorylation of tyrosyl residues on c-Met, a cascade of tyrosine phosphorylations on several other proteins and activation of microtubule-associated protein kinase/extracellular signal-regulated kinase. Met expression and activity are normal in human melanomas, and constitutive activity of HGF/SF in retrovirally infected autonomously proliferative mouse melanocytes is insufficient to confer the malignant phenotype. Our findings suggest that activation of Met in response to HGF/SF may contribute to malignant progression synergistically with the aberrant expression of bFGF in malignant melanocytes and that, in addition, the peptide may promote dispersion of factor-dependent melanocytes from early stages of primary melanomas to ectopic sites.

Original languageEnglish (US)
Pages (from-to)2195-2206
Number of pages12
JournalOncogene
Volume7
Issue number11
Publication statusPublished - Nov 1992

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ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Halaban, R., Rubin, J. S., Funasaka, Y., Cobb, M., Boulton, T., Faletto, D., ... Moellmann, G. (1992). Met and hepatocyte growth factor/scatter factor signal transduction in normal melanocytes and melanoma cells. Oncogene, 7(11), 2195-2206.