Fas receptor and TRAIL receptors (Fas (CD95, APO-1), TRAIL-R1 (DR4), TRAIL-R2 (DR5))

The Fas receptor (CD95, APO-1) and TRAIL receptors (TRAIL-R1/DR4, TRAIL-R2/DR5) are cell surface members of the tumor necrosis factor (TNF) receptor superfamily involved in the regulation of apoptosis, especially in the immune response and tumor surveillance[1][3][6][7]. Fas ligand (FasL) binds Fas receptor, while TRAIL (TNF-related apoptosis-inducing ligand) binds to TRAIL-R1 and TRAIL-R2, inducing apoptosis via recruitment of the adaptor protein FADD and subsequent activation of caspase-8, leading to cell death. Additional decoy receptors (TRAIL-R3/DcR1 and TRAIL-R4/DcR2) bind TRAIL but lack a functional death domain, acting as competitive inhibitors of apoptosis. In cancer, tumors may resist FasL- and TRAIL-induced apoptosis and, under some conditions, can utilize these pathways for cell migration, invasion, or non-death signaling, often in the presence of oncogenic mutations such as K-Ras[2][4]. Therapeutic targeting of these receptors aims to selectively induce apoptosis in tumor cells, but challenges include resistance mechanisms, paradoxical prosurvival signaling, and safety concerns.

Other names

Fas: CD95, APO-1, TNFRSF6Fas ligand: FasL, CD95L, TNFSF6TRAIL: TNF-related apoptosis-inducing ligand, Apo2L, TNFSF10TRAIL-R1: DR4, TNFRSF10ATRAIL-R2: DR5, TNFRSF10BTRAIL-R3: DcR1, TNFRSF10CTRAIL-R4: DcR2, TNFRSF10D

Induction of apoptosis via formation of death-inducing signaling complex (DISC) Activation of caspase-8 and downstream apoptosis cascade Inhibition of survival pathways (e.g., via antagonists or ligand sequestration) Non-apoptotic (pro-survival, pro-migratory) signaling in some cancer contexts