Rho regulates the hepatocyte growth factor/scatter factor-stimulated cell motility of human oral squamous cell carcinoma cells.
To investigate the effects of hepatocyte growth factor/scatter factor (HGF/SF) on the invasion and metastasis of human oral squamous cell carcinoma (SCC) cells, we examined cell motility and intercellular signal transduction of a human oral SCC cell line (SAS) obtained from the primary lesion of a tongue carcinoma. HGF/SF stimulation significantly enhanced the motility of SAS cells in a dose-dependent manner. Clostridium botulinum C3 exoenzyme (C3), which is known to selectively impair the function of Ras-related small G-protein p21rho (Rho), significantly reduced the motility of SAS cells. HGF/SF stimulation also enhanced the tyrosine phosphorylation of HGF receptors (c-Met) and focal adhesion kinase (FAK) on SAS cells, but C3 completely inhibited the phosphorylation of FAK. Furthermore, it was observed that Rho A protein, normally located around the nuclear area, was translocated to the membrane and levels in the cytolysate increased following HGF/SF stimulation with no change in Rho A mRNA. These results suggest that the activation of FAK caused by phosphorylation of c-Met may mediate the HGF/SF-induced motility of human oral SCC cells, and that Rho protein regulates the tyrosine phosphorylation of FAK through translocation from the nucleus to the membrane.
Kitajo
Hiroyuki
H
Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido, Tobetsu, Ishikari, Hokkaido 061-0293, Japan.
Shibata
Toshiyuki
T
Nagayasu
Hiroki
H
Kawano
Takashi
T
Hamada
Jun-Ichi
J
Yamashita
Tomomi
T
Arisue
Makoto
M
D036002:ADP Ribose Transferases / Q000494:pharmacology; D015153:Blotting, Western; D001905:Botulinum Toxins / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D009062:Mouth Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D014443:Tyrosine; D017228:Hepatocyte Growth Factor; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D011505:Protein-Tyrosine Kinases; D019859:Proto-Oncogene Proteins c-met; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D001905:Botulinum Toxins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein