LOW CONCENTRATIONS OF THE PHOSPHATASE INHIBITOR OKADAIC ACID STOP TUMOR-CELL LOCOMOTION

The phosphatase inhibitor okadaic acid exerted a biphasic effect on th e shape of spontaneously polarized Walker carcinosarcoma cells. At low er concentrations, the drug suppressed cell polarity (IC50 = 0.14 mu M ) and the cells reverted to a spherical shape. At higher concentration s (> 0.25 mu M), cells developed large blebs (IC50 = 0.4 mu M). Furthe rmore, 0.2 mu M okadaic acid completely suppressed spontaneous cell lo comotion. Two specific inhibitors of protein kinase C did not prevent the actions of okadaic acid on cell shape, showing that this enzyme is very likely not involved. Another phosphatase inhibitor, calyculin A, also suppressed polarity (IC50 = 60 nM) and produced blebbing cells ( IC50 = 70 nM). 1 mu M okadaic acid induced a 40- to 70-fold increase i n phosphorylation of the intermediate filament protein vimentin in int act cells. Increased phosphorylation of this major phosphoprotein corr elated with the generation of blebbing cells, rather than with inhibit ion of polarity and may thus be involved in generating the marked shap e chances. We conclude that constitutive phosphatase activity is requi red for motility and control of shape in Walker carcinosarcoma cells. (C) 1997 Elsevier Science B.V.