Lung cancer A549 cells migrate directionally in DC electric fields with polarized and activated EGFRs.

Endogenous direct-current electric fields (dcEFs) occur in vivo in the form of epithelial transcellular potentials or neuronal field potentials. A variety of cells respond to dcEFs by migrating directionally, and this is termed galvanotaxis. The mechanism by which dcEFs direct cell movement, however, is not yet understood, and the effects on lung cancer cells are entirely unknown. We demonstrated that cultured human lung adenocarcinoma A549 cells migrate toward the cathode in applied dcEFs at 3 V/cm. Fluorescence microscopy showed that both epidermal growth factor receptors (EGFRs) and F-actin are polarized to the cathode. EGFR inhibitors, cetuximab and AG1478, reduced the migration rate and directed motility in dcEFs. Western blots showed that ERK and AKT signaling pathways were prominently promoted by dcEFs. EGFR inhibitors could reduce this promotion but not completely. These data suggest that polarization of EGFRs and the activation of their downstream signals play an important role in the galvanotaxis of A549 cells in dcEFs. (c) 2008 Wiley-Liss, Inc.