Lysophosphatidic acid promotes phorbol-ester-induced apoptosis in TF-1 cells by interfering with adhesion

When exposed to PMA, the erythroblastic cell line TF-1 and its cytokine-ind ependent variant D2 cells can be induced to undergo differentiation and apo ptosis. In this study we investigated the mechanism responsible for the dif ferential responses to PMA induction and show that serum present in the med ium has a major role in promoting PMA-induced apoptosis in TF-1 and D2 cell s. Interestingly, lysophosphatidic acid (LPA) could replace serum to co-ope rate with PMA in inducing apoptosis via the Rho-dependent pathway. The expr ession of a constitutively active form of RhoA also increased PMA-induced a poptosis, However, by inhibiting adhesion, most cells underwent PMA-induced apoptosis even in the absence of LPA or serum, indicating that adhesion is required for PMA-induced differentiation. Given that LPA could prevent adh esion for cells maintained in the serum-free medium, here we propose that R hoA has a switching role in determining whether TF-1 and D2 cells undergo d ifferentiation or apoptosis in response to PMA by modulating cell adhesion.