The relevance of NF-?B for CD95 Signaling in Tumor Cells

Most members of the death receptor family including CD95 (APO-1/Fas) have beenshown to induce both apoptosis as well as nonapoptotic pathways depending on thetissue and the circumstances. One of the nonapoptotic pathways emanating from CD95,activation of NF-?B, has recently been demonstrated to regulate invasiveness ofapoptosis resistant tumor cells. In contrast, activation of NF-?B in apoptosing cells isbelieved to be suppressed due to cleavage of various NF-?B pathway components byactive caspases that execute apoptosis. We now present data demonstrating that incertain highly CD95 apoptosis sensitive cells NF-?B is robustly activated. In factoverexpression of apoptosis inhibitors such as Bcl-2 or c-FLIPL in these cells results indecreased activation of NF-?B through CD95. We propose a model in which NF-?B isgenerally activated in certain cells but may have different functions depending onwhether cells are programmed to die or to survive.