Abstract:
:Although evasion of apoptosis is thought to be required for the development of cancer, it is unclear which cell death pathways are evaded. We previously identified a novel epithelial cell death pathway that works in normal cells but is inactivated in tumor cells, implying that it may be targeted during tumor development. The pathway can be activated by the Fas-associated death domain (FADD) of the adaptor protein but is distinct from the known mechanism of FADD-induced apoptosis through caspase-8. Here, we show that a physiological signal (tumor necrosis factor-related apoptosis-inducing ligand) can kill normal epithelial cells through the endogenous FADD protein by using the novel FADD death domain pathway, which activates both apoptosis and autophagy. We also show that selective resistance to this pathway occurs when primary epithelial cells are immortalized and that this occurs through a mechanism that is independent of known events (telomerase activity, and loss of function of p53, Rb, INK4a, and ARF) that are associated with immortalization. These data identify a novel cell death pathway that combines apoptosis and autophagy and that is selectively inactivated at the earliest stages of epithelial cancer development.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Thorburn J,Moore F,Rao A,Barclay WW,Thomas LR,Grant KW,Cramer SD,Thorburn Adoi
10.1091/mbc.e04-10-0906keywords:
subject
Has Abstractpub_date
2005-03-01 00:00:00pages
1189-99issue
3eissn
1059-1524issn
1939-4586pii
E04-10-0906journal_volume
16pub_type
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