Rho regulates the hepatocyte growth factor/scatter factor-stimulated cell motility of human oral squamous cell carcinoma cells |
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Authors: | Kitajo Hiroyuki Shibata Toshiyuki Nagayasu Hiroki Kawano Takashi Hamada Jun-Ichi Yamashita Tomomi Arisue Makoto |
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Institution: | Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido, Tobetsu, Ishikari, Hokkaido 061-0293, Japan. |
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Abstract: | 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. |
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