Inhibition of EGF-induced cytoskeletal change in A431 cells by inhibitors of phosphatidylinositol turnover.

Expression of epidermal growth factor (EGF) receptor is often increased in various human carcinomas. Therefore, inhibition of the EGF/EGF receptor-induced signaling pathway may help to suppress these carcinomas. In the presence of Ca2+, EGF induces elongation of A431 cells in approximately 30 min. The cell elongation was shown to be accompanied by a reorganization of actin filaments. These phenotypical changes were specifically inhibited by a tyrosine kinase inhibitor, erbstatin, and inhibitors of phosphatidylinositol (PI) turnover such as psi-tectorigenin and inostamycin. The amount of filamentous actin was increased by EGF, which was also inhibited by these compounds. Long-term treatment of A431 cells with EGF induced the disappearance of cytoskeleton and aggregation of the cells, which was again inhibited by the PI turnover inhibitors. Thus tyrosine kinase and phosphatidylinositol turnover inhibitors were shown to inhibit the signaling pathways of EGF-induced cytoskeletal organization of A431 cells.