Atypical Chemokine Receptors in Cancer

Chemokines or chemoattractant cytokines are a superfamily of small (8-12 kDa) secreted proteins. They primarily promote and regulate the directional migration and trafficking of the cells. Approximately 50 chemokine ligands and 20 chemokine receptors have been identified in humans. These molecules constitute a complex network of ligand-receptor interactions. Generally, upon binding a chemokine receptor to its cognate ligand, a signaling pathway is induced via G protein coupling to the receptor. However, because of the modified DRYLAIV motif in the second intracellular loop, atypical chemokine receptors do not couple with G proteins and do not induce signal transduction. Up to date, five decoy chemokine receptors have been identified; namely, DARC, D6, CXCR7, CCX-CKR, and CCRL2. Except CXCR7, other decoy chemokine receptors regulate cell migration by sequestering their cognate chemokine ligands. This review focuses on atypical chemokine receptors that play important roles in cancer.