Forced expression of NESH suppresses motility and metastatic dissemination of malignant cells.
To characterize the function of a novel Src homology 3 (SH3) adapter protein termed NESH, we have established transfectants stably expressing NESH. We observed that every clone of NESH transfectants caused a marked reduction in motility, although the clones exhibited no significant differences in intrinsic cell growth compared with the control cells in vitro. The NESH transfectants also exhibited significant reduction in tumor metastatic potential in vivo. We found that NESH expression is frequently lost in invasive cancer cell lines despite its ubiquitous expression in normal tissues. The SH3 domain of NESH seems to interact with p21-activated kinase (PAK), which is involved in regulation of cell motility. Furthermore, a significant decrease in PAK phosphorylation at (402)Thr was found in NESH transfectants. Taken together, these results suggest that NESH inhibits ectopic metastasis of tumor cells as well as cell migration through interaction with intracellular molecules such as PAK that are essential for cell motility.
Ichigotani
Yasukatu
Y
Department of Molecular Pathogenesis, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Yokozaki
Shouichi
S
Fukuda
Yoshihide
Y
Hamaguchi
Michinari
M
Matsuda
Satoru
S
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D054462:p21-Activated Kinases; D018909:src Homology Domains / Q000235:genetics / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C000605635:Abi-3 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020558:GTP Phosphohydrolases