We examined the effects of transforming growth factor
β1 (TGF
β1) on cellular functions in human lung cancer cell line A549. Treatment of A549 cells with 1 ng/ml TGF
β1 for more than 3 days altered their morphology from an epithelial cobblestone-like appearance to a fibroblast-like one, reduced the expression of E-cadherin mRNA and protein, and induced the formation of F-actin fibers. These hallmarks indicate that TGF
β1 induced the epithelial–mesenchymal transition in A549 cells. Migration of TGF
β1-treated A549 cells, which was quantified by the wound-healing assay, was markedly accelerated by 3
μM ATP
γS, a non-hydrolyzable ATP analogue. ATP
γS-induced migration of TGF
β1-treated A549 cells was reversed by the P2 antagonist suramin. In contrast, migration of control A549 cells was not altered by ATP
γS. TGF
β1-treated A549 cells showed an augmentation of ATP-induced Ca
2+ transients, thapsigargin-induced Ca
2+ transients, and store-operated Ca
2+ entry compared with those in control cells. Basal level of the extracellular ATP concentration was significantly lower in TGF
β1-treated A549 cells than in control cells. We conclude from these results that TGF
β1 augments ATP-induced Ca
2+ mobilization, which leads to the acceleration of migration, in A549 cells but, it markedly reduces endogenous ATP release. This implies that the actions of ATP would become a novel therapeutic target for inhibiting cancer cell migration.
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