DcR2

DcR2, also known as TRAIL receptor 4 and TNFRSF10D, is a member of the tumor necrosis factor receptor (TNFR) superfamily. It functions as a decoy receptor for the TNF-related apoptosis-inducing ligand (TRAIL).

TRAIL can bind death receptors DR4 and DR5 to initiate caspase cascades leading to apoptosis. DcR2 binds TRAIL but does not propagate a death signal because it lacks a functional cytoplasmic death domain.

By sequestering TRAIL, DcR2 can compete with DR4 and DR5, reducing TRAIL-induced apoptosis in cells expressing DcR2. The relative expression of DcR2 and death receptors can influence cellular sensitivity to TRAIL.

DcR2 is expressed in several normal tissues and is frequently upregulated in various cancers. Regulation occurs at the transcriptional and epigenetic levels, and the balance of DcR2 with DR4/DR5 can influence responses to TRAIL-based therapies. Some studies suggest that high DcR2 expression correlates with resistance to TRAIL-induced cell death and may contribute to tumor cell survival.

From a therapeutic perspective, DcR2 is a potential target to improve TRAIL-based anticancer strategies; approaches include downregulation of DcR2 or blocking its interaction with TRAIL to enhance tumor cell killing. However, clinical application remains under investigation, and DcR2’s role can vary among tumor types.