Differences and Similarities in TRAIL- and Tumor Necrosis Factor-Mediated Necroptotic Signaling in Cancer Cells

摘要: Recently, a type of regulated necrosis (RN) called necroptosis was identified to be involved in many pathophysiological processes and emerged as an alternative method eliminate cancer cells. However, only few studies have elucidated components TRAIL-mediated useful for anticancer therapy. Therefore, we compared this cell death tumor factor (TNF)-mediated found similar signaling through acid neutral sphingomyelinases, the mitochondrial serine protease HtrA2/Omi, Atg5, vacuolar H(+)-ATPase. Notably, executive mechanisms both TRAIL- TNF-mediated are independent poly(ADP-ribose) polymerase 1 (PARP-1), depletion p38α increases levels types death. Moreover, differences between TNF- necroptosis, e.g., lack involvement ubiquitin carboxyl hydrolase L1 (UCH-L1) Atg16L1 necroptosis. Furthermore, discovered indications altered components, since overexpression protein Bcl-2 protected Jurkat cells from Bcl-XL diminished TRAIL-induced Colo357 TRAIL does not require receptor internalization endosome-lysosome acidification mediate Taken together, pathways described those might unique targets increase or modify necroptotic more specifically future approaches.