Functions and mechanisms of chemokine receptor 7 in tumors of the digestive system

Chemokine (C-X-C motif) receptor 7 (CXCR7), recently termed ACKR3, belongs to the G protein-coupled cell surface receptor family, binds to stromal cell-derived factor-1 [SDF-1, or chemokine (C-X-C motif) ligand 12] or chemokine (C-X-C motif) ligand 11, and is the most common chemokine receptor expressed in a variety of cancer cells. SDF-1 binds to its receptor chemokine (C-X-C motif) receptor 4 (CXCR4) and regulates cell proliferation, survival, angiogenesis and migration. In recent years, another new receptor for SDF-1, CXCR7, has been discovered, and CXCR7 has also been found to be expressed in a variety of tumor cells and tumor-related vascular endothelial cells. Many studies have shown that CXCR7 can promote the growth and metastasis of a variety of malignant tumor cells. Unlike CXCR4, CXCR7 exhibits a slight modification in the DRYLAIV motif and does not induce intracellular Ca²⁺ release following ligand binding, which is essential for recruiting and activating G proteins. CXCR7 is generally thought to work in three ways: (1) Recruiting β-arrestin 2; (2) Heterodimerizing with CXCR4; and (3) Acting as a "scavenger" of SDF-1, thus lowering the level of SDF-1 to weaken the activity of CXCR4. In the present review, the expression and role of CXCR7, as well as its prognosis in cancers of the digestive system, were investigated.