PMID- 12883706 OWN - NLM STAT- MEDLINE DCOM- 20040421 LR - 20131121 IS - 1021-335X (Print) IS - 1021-335X (Linking) VI - 10 IP - 5 DP - 2003 Sep-Oct TI - Rho regulates the hepatocyte growth factor/scatter factor-stimulated cell motility of human oral squamous cell carcinoma cells. PG - 1351-6 AB - 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. FAU - Kitajo, Hiroyuki AU - Kitajo H AD - Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido, Tobetsu, Ishikari, Hokkaido 061-0293, Japan. FAU - Shibata, Toshiyuki AU - Shibata T FAU - Nagayasu, Hiroki AU - Nagayasu H FAU - Kawano, Takashi AU - Kawano T FAU - Hamada, Jun-Ichi AU - Hamada J FAU - Yamashita, Tomomi AU - Yamashita T FAU - Arisue, Makoto AU - Arisue M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 42HK56048U (Tyrosine) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.4.2.- (ADP Ribose Transferases) RN - EC 2.4.2.- (exoenzyme C3, Clostridium botulinum) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 2.7.10.2 (Focal Adhesion Kinase 1) RN - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (PTK2 protein, human) RN - EC 3.4.24.69 (Botulinum Toxins) RN - EC 3.6.5.2 (rho GTP-Binding Proteins) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) SB - IM MH - ADP Ribose Transferases/pharmacology MH - Blotting, Western MH - Botulinum Toxins/pharmacology MH - Carcinoma, Squamous Cell/*metabolism MH - Cell Line, Tumor MH - Cell Membrane/metabolism MH - Cell Movement MH - Cell Nucleus/metabolism MH - Dose-Response Relationship, Drug MH - Focal Adhesion Kinase 1 MH - Focal Adhesion Protein-Tyrosine Kinases MH - Hepatocyte Growth Factor/*metabolism MH - Humans MH - Microscopy, Confocal MH - Mouth Neoplasms/*metabolism MH - Phosphorylation MH - Precipitin Tests MH - Protein Transport MH - Protein-Tyrosine Kinases/metabolism MH - Proto-Oncogene Proteins c-met/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Time Factors MH - Tyrosine/metabolism MH - rho GTP-Binding Proteins/metabolism/*physiology MH - rhoA GTP-Binding Protein/metabolism EDAT- 2003/07/29 05:00 MHDA- 2004/04/22 05:00 CRDT- 2003/07/29 05:00 PHST- 2003/07/29 05:00 [pubmed] PHST- 2004/04/22 05:00 [medline] PHST- 2003/07/29 05:00 [entrez] PST - ppublish SO - Oncol Rep. 2003 Sep-Oct;10(5):1351-6.