The tumor necrosis factor related apoptosis-inducing ligand (TRAIL) is a cytokine involved in the modulation of cell survival in different cell models. Similarly to other tumor necrosis factor (TNF) family members, TRAIL mediates apoptosis by binding to two receptors, DR4 and DR5, with a common structural organization characterized by an extracellular cysteinerich domain required for ligand bin...

The apparent tumour selective apoptosis inducing activity of recombinant soluble TRAIL has aroused much interest for use in clinical application. However, to fully exploit its therapeutic potential the characteristics of both the TRAIL receptor system and sTRAIL should be taken into account. Firstly, the wide spread expression of the various TRAIL receptors throughout the human body; secondly, ...

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors are promising targets for the selective eradication of tumor cells while sparing normal cells. Currently, both recombinant TRAIL proteins and TRAIL receptor agonistic antibodies are being tested in the clinic, showing encouraging antitumor activities and mild side effects. Unfortunately, resistance to TRAIL therapy is fre...

We previously observed that TRAIL induces acquired TRAIL resistance coinciding with increased Akt phosphorylation brought about by the Src-PI3K-Akt signaling pathways and mediated by c-Cbl. c-Cbl, a ubiquitously expressed cytoplasmic adaptor protein, is simultaneously involved in the rapid degradation of TRAIL receptors and Akt phosphorylation during TRAIL treatment. Here, we show that Akt phos...

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a tumor necrosis factor superfamily member, targets death receptors and selectively kills malignant cells while leaving normal cells unaffected. However, unlike most cancers, many osteosarcomas are resistant to TRAIL. To investigate this resistance, we characterized the response of MG-63 osteosarcoma cells and hPOB-tert osteoblast...

Endothelial cell survival and antiapoptotic pathways, including those stimulated by extracellular matrix, are critical regulators of vasculogenesis, angiogenesis, endothelial repair, and shear-stress-induced endothelial activation. One of these pathways is mediated by alpha(v)beta(3) integrin ligation, downstream activation of nuclear factor-kappaB, and subsequent up-regulation of osteoproteger...

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anticancer agent that selectively induces apoptosis in a variety of cancer cells by interacting with death receptors DR4 and DR5. TRAIL can also bind to decoy receptors (DcR1, DcR2, and osteoprotegerin receptor) that cannot induce apoptosis. Different tumor types respond either to DR4 or to DR5 activation, and chemot...

Tumor necrosis-factor related apoptosis-inducing ligand, also known as TRAIL or APO2L (Apo-2 ligand), is a cytokine of the TNF superfamily acknowledged for its ability to trigger selective apoptosis in tumor cells while being relatively safe towards normal cells. Its binding to its cognate agonist receptors, namely death receptor 4 (DR4) and/or DR5, can induce the formation of a membrane-bound ...

TRAIL induces apoptotic cell death upon binding to either of two proapoptotic TRAIL receptors, TRAIL R1 (DR4) or TRAIL R2 (KILLER/DR5). Activation of the proapoptotic death receptors by TRAIL engagement induces the formation of a death-inducing signaling complex (DISC), which consists of receptor, FADD, as an adaptor, and caspase 8 as an initiator caspase. Once the DISC is formed, the caspase 8...

Metabolic stress occurs frequently in tumors and in normal tissues undergoing transient ischemia. Nutrient deprivation triggers, among many potential cell death-inducing pathways, an endoplasmic reticulum (ER) stress response with the induction of the integrated stress response transcription factor ATF4. However, how this results in cell death remains unknown. Here we show that glucose deprivat...