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.

Cell detachment triggers p38 mitogen-activated protein kinase-dependent overexpression of fas ligand: A novel mechanism of anoikis of intestinal epithelial cells / Rosen, K.; Shi, W.; Calabretta, Bruno; F. i. l. m. u. s., J.. - In: JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 1083-351X. - STAMPA. - 277:48(2002), pp. 46123-46130. [10.1074/jbc.M207883200]

Cell detachment triggers p38 mitogen-activated protein kinase-dependent overexpression of fas ligand: A novel mechanism of anoikis of intestinal epithelial cells

CALABRETTA, Bruno;
2002

Abstract

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.
2002
277
48
46123
46130
Cell detachment triggers p38 mitogen-activated protein kinase-dependent overexpression of fas ligand: A novel mechanism of anoikis of intestinal epithelial cells / Rosen, K.; Shi, W.; Calabretta, Bruno; F. i. l. m. u. s., J.. - In: JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 1083-351X. - STAMPA. - 277:48(2002), pp. 46123-46130. [10.1074/jbc.M207883200]
Rosen, K.; Shi, W.; Calabretta, Bruno; F. i. l. m. u. s., J.
File in questo prodotto:
File Dimensione Formato  
PIIS0021925819332156.pdf

Open access

Tipologia: Versione pubblicata dall'editore
Dimensione 521.67 kB
Formato Adobe PDF
521.67 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/20926
Citazioni
  • ???jsp.display-item.citation.pmc??? 31
  • Scopus 75
  • ???jsp.display-item.citation.isi??? 70
social impact