Protein phosphatases 1 and 2A maintain endothelial cells in a resting state, limiting the motility that is needed for the morphogenic process of angiogenesis

Angiogenesis that is induced by cancers, including those of the head and neck, requires endothelial cells to shift from a nonmotile resting state to an increased level of motility. Using a human microvascular endothelial cell line, this study shows the importance of the serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A) in restricting endothelial cell motility. Treatment of endothelial cells with increasing concentrations of the PP1 and PP2A inhibitor okadaic acid resulted in cell rounding and increased motility, which was accompanied by cytoskeletal disorganization involving a loss of filamentous beta-tubulin and F-actin. These effects occurred at okadaic acid levels that selectively inhibit PP2A and became more prominent with higher levels that inhibit both PP2A and PP1. This study shows the importance of PP1 and PP2A in maintaining cytoskeletal organization, thereby limiting endothelial cell motility, and suggests that pharmacologic approaches to enhance PP1 and PP2A activities may be useful in preventing key events of the angiogenic process.