The death receptor TRAIL in cancer cell apoptosis

Abstract

Apoptosis is a key regulator or tissue homeostasis. Death ligands and death receptors of the tumor necrosis factor (TNF) family play crucial roles in mediating apoptosis. TNF-related apoptosis-inducing ligand (TRAIL) is unique amongst death ligands in that it uniquely induces apoptosis in transformed cells, but not normal cells. Indeed, TRAIL is being developed as an anticancer therapy. However, many malignant tumors are resistant to apoptosis induction by TRAIL. Understanding the mechanism of resistance to TRAIL-mediated apoptosis will not only provide insight regarding transduction of the death signal, but will also be essential for designing strategies to overcome resistance to TRAIL for clinical applicatons. In this review, we focus on the apoptosis signaling pathways stimulated by TRAIL, and summarize recent clues regarding TRAIL physiology.