PMID: 7527397Dec 16, 1994Paper

Hepatocyte growth factor/scatter factor induces tyrosine phosphorylation of focal adhesion kinase (p125FAK) and promotes migration and invasion by oral squamous cell carcinoma cells

The Journal of Biological Chemistry
K MatsumotoR H Kramer

Abstract

Fibroblasts or their conditioned medium stimulated invasion by squamous cell carcinoma cells. The fibroblast-derived activity responsible for increased invasion is the hepatocyte growth factor/scatter factor (HGF/SF), a ligand for the c-Met receptor. HGF/SF stimulated migration of the cells on various extracellular matrix substrates but did not alter their adhesion efficiency nor integrin expression. HGF/SF stimulated motility in a two step process: initially cells spread rapidly and formed focal adhesions, and then they disassembled these condensations, which was followed by increased cell locomotion. The focal adhesions contained vinculin, p125FAK, beta 1 integrin, and phosphotyrosine. Within minutes after exposure of cells to HGF/SF, proteins of 125 and 145 kDa showed elevated tyrosine phosphorylation and were identified as p125FAK and c-Met, respectively. Gradual loss of tyrosine phosphorylation coincided with disruption of focal adhesions and conversion to a motile phenotype. HGF/SF-mediated tyrosine phosphorylation of p125FAK was inhibited by the tyrosine kinase inhibitor, herbimycin A, which also blocked spreading and the migratory response. These results indicate that fibroblast-derived HGF/SF triggers migration through...Continue Reading

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