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-independent variant D2 cells can be induced to undergo differentiation and apoptosis. In this study we investigated the mechanism responsible for the differential responses to PMA induction and show that serum present in the medium has a major role in promoting PMA-induced apoptosis in TF-1 and D2 cells. Interestingly, lysophosphatidic acid (LPA) could replace serum to co-operate with PMA in inducing apoptosis via the Rho-dependent pathway. The expression of a constitutively active form of RhoA also increased PMA-induced apoptosis. 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 adhesion for cells maintained in the serum-free medium, here we propose that RhoA has a switching role in determining whether TF-1 and D2 cells undergo differentiation or apoptosis in response to PMA, by modulating cell adhesion.
Lai
J M
JM
Institute of Biochemistry, College of Medicine, National Taiwan University, College of Medicine, No. 1 Jen-Ai Road, Section 1, Taipei, Taiwan, ROC.
Lu
C Y
CY
Yang-Yen
H F
HF
Chang
Z F
ZF
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D023461:Myeloid Progenitor Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011493:Protein Kinase C / Q000378:metabolism; D021381:Protein Transport; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014162:Transfection; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D002273:Carcinogens; D008246:Lysophospholipids; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011493:Protein Kinase C; D020742:rhoA GTP-Binding Protein; D013755:Tetradecanoylphorbol Acetate