Human Chemokine C-X-C-Motif Receptor 7 (CXCR7) Protein

Background

ACKR3, also known as CXCR7, is an atypical chemokine receptor that binds CXCL12 and CXCL11 but does not trigger classical G protein signaling. Instead, it functions as a "scavenger receptor," internalizing and degrading chemokines to regulate their extracellular levels. ACKR3 is expressed on endothelial cells, smooth muscle cells, and cancer cells and plays a critical role in modulating chemokine gradients, which control immune cell migration. In cancer, ACKR3 is frequently overexpressed and promotes tumor growth, survival, and metastasis by scavenging CXCL12, enhancing CXCR4-mediated signaling. It is involved in glioblastoma, breast, and prostate cancers, where its expression correlates with poor prognosis and therapy resistance. ACKR3 also contributes to angiogenesis by promoting endothelial cell migration and tube formation. In the central nervous system, it regulates CXCL12 availability, impacting neurogenesis and neuronal repair. While it does not induce typical signaling, ACKR3 activates β-arrestin-dependent pathways that influence cellular adhesion, survival, and proliferation. Its atypical signaling and scavenging activity make ACKR3 an attractive target for cancer therapy and inflammatory disease treatment.