Many cell types undergo apoptosis when they are detached from the extracellular matrix (ECM). This phenomenon has been termed anoikis. Most epithelial cells, which are normally attached to a type of ECM called basement membrane, are particularly sensitive to anoikis. Conversely, carcinoma cells tend to be resistant to anoikis, and this resistance plays a critical role in tumor invasion and metastasis. We reported previously that detachment-induced down-regulation of the anti-apoptotic molecule Bcl-XLmakes a significant contribution to anoikis of intestinal epithelial cells. Here we demonstrate that exogenous Bcl-XL, no matter how highly expressed in these cells, can significantly attenuate anoikis but cannot completely prevent it, suggesting that at least another pro-apoptotic event is activated by the loss of cell-ECM contacts. Indeed, in this study we identified a novel mechanism of anoikis in intestinal epithelial cells that involves detachment-induced overexpression of Fas ligand. We also demonstrated that this elevation in Fas ligand expression requires a detachment-induced increase of p38 mitogen-activated protein kinase activity. We conclude that the activation of at least two different pro-apoptotic events is required for anoikis of intestinal epithelial cells.
|Anno di pubblicazione:||2002|
|Titolo:||Cell detachment triggers p38 MAP Kinase-dependent overexpression of FAS ligand: a novel mechanism of anoikis in intestinal epithelial cells.|
|Autore/i:||Rosen; K.; Shi W.; Calabretta B.; Filmus. J.|
|Tipologia||Articolo su rivista|
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