herbimycin and Mouth-Neoplasms

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 the initial recruiting of integrins, cytoskeletal proteins, and p125FAK into focal adhesions that is dependent on tyrosine kinase activity.

Topics: Benzoquinones; Carcinoma, Squamous Cell; Cell Adhesion; Cell Adhesion Molecules; Cell Movement; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Hepatocyte Growth Factor; Humans; In Vitro Techniques; Integrins; Lactams, Macrocyclic; Mouth Neoplasms; Neoplasm Invasiveness; Phosphotyrosine; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-met; Quinones; Receptor Protein-Tyrosine Kinases; Rifabutin; Tumor Cells, Cultured; Tyrosine