Downregulating PRL-3 inhibit migration and invasion of lung cancer cell via RhoA and mDia1.

AIMS AND BACKGROUND The overexpression of phosphatase of regenerating liver-3 (PRL-3) affects the migration and invasion of epithelial cells. Little is known about the substrates or pathways that PRL-3 interacts with. METHODS We studied the action and the mechanism of PRL-3 in migration and invasion of lung cancer. We detected the expression of PRL-3 in lung cancer cell lines and normal human bronchial epithelial cell. RESULTS We found that PRL-3 expression was high in lung cancer cells. Knockdown of PRL-3 by siRNA inhibited cell migration and invasion and reorganizated the cytoskeleton. Furthermore, blocking PRL-3 decreased RhoA activity and mDia1 expression. Blocking RhoA or mDia1 showed the similar changes of cytoskeleton and suppression of migration and invasion as inhibiting PRL-3 expression. Blocking RhoA inhibited the expression of mDia1. CONCLUSIONS These data indicate that downregulating PRL-3 inhibit cell migration and invasion by inactivating RhoA to downregulate mDia1 to reorganizate cytoskeleton of lung cancer cells.