The relevance of NF-kappaB for CD95 signaling in tumor cells.
Most members of the death receptor family including CD95 (APO-1/Fas) have been shown to induce both apoptosis as well as non-apoptotic pathways depending on the tissue and the circumstances. One of the non-apoptotic pathways emanating from CD95, activation of NF-kappaB, has recently been demonstrated to regulate invasiveness of apoptosis resistant tumor cells. In contrast, activation of NF-kappaB in apoptosing cells is believed to be suppressed due to cleavage of various NF-kappaB pathway components by active caspases that execute apoptosis. We now present data demonstrating that in certain highly CD95 apoptosis sensitive cells NF-kappaB is robustly activated. In fact overexpression of apoptosis inhibitors such as Bcl-2 or c-FLIPL in these cells results in decreased activation of NF-kappaB through CD95. We propose a model in which NF-kappaB is generally activated in certain cells but may have different functions depending on whether cells are programmed to die or to survive.
The Ben May Institute for Cancer Research, Committees on Immunology and Cancer Biology, The University of Chicago, Chicago, Illinios 60637, USA.
Patrick
P
Legembre
Bryan C
BC
Barnhart
Marcus E
ME
Peter
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism*
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D019014:fas Receptor