EGF receptor (EGFR) mediated cell motility is a complex process which involves transduction of motility specific signals, modification of the actin cytoskeleton, and cell - ECM interactions. FAC and cell adhesiveness play a major role in cell motility. However, the mechanism by which EGF receptor-mediated signals alter FAC integrity and cell adhesiveness is still poorly defined. We utilized NR6 fibroblasts expressing wild type EGFR to investigate whether EGFR activation can alter the interface interaction between cell and ECM. EGFR signaling decreased the fraction of cells presenting FAC from 60% to less than 30%. The disassembly of FAC was noticeable by 5 minutes, maximal by 20 minutes, and maintained for at least 12 hours. This result parallels with our previous finding that EGFR mediates increased cell motility through activated PLC-γ pathway. The PLC-γ specific inhibitor drug U-73122 did not prevent the reduction of decreased population of cells with FAC. These results may indicate that EGFR mediated cell motility requires both PLC-γ dependent actin reorganization and PLC-γ independent modification of cell - substratum interaction. Our preliminary experiments support the hypothesis that the EGFR- mediated signaling may optimize cell motility by decreasing FAC in order to achieve a delicate balance between motogenic force and cell traction. Further experiments will map the pathway from EGF receptor to focal adhesion and compare the adhesive asstrength of FAC positive and FAC negative cells.