CXCR1

CXCR receptors (C-X-C Motif Chemokine Receptors) are a family of chemokine receptors that belong to the group of G-protein-coupled receptors (GPCRs). Chemokine receptors are 7-transmembrane G-protein-coupled receptors that are activated by the binding of one or more chemokines.

CXCR receptors play an essential role in the immune system by influencing the migration of immune cells to sites of inflammation or to tissues. Chemokines are signaling molecules produced by various cells. They form a family of chemoattractive molecules, of which more than 50 have been identified to date. Chemokines are categorized into four main groups according to the number and spacing of conserved cysteines: CXC, CC, CX3C and C. They bind to their specific receptors (e.g. CXCR) and thus initiate a signaling cascade that controls the behavior of immune cells, including their movement, activation and differentiation. In individual cases, this can also influence tumor growth.

CXCR1 binds to the chemokine interleukin-8 (also known as C-X-C motif ligand 8 or CXCL8) (Liu Q et al. 2016).CXCR1 plays a role in the recruitment of neutrophil granulocytes to sites of inflammation. Interleukin-8 only exerts its effect by binding to the receptors CXCR1 and CXCR2, which are mainly found in neutrophils, monocytes and endothelial cells. The G-protein heterotrimer (alpha, beta, gamma subunits) binds constitutively to the CXCR1/CXCR2 receptor. Activation by IL8 leads to activation of multiple downstream signaling pathways, including PI3K and MAPK pathways. The CXCL8-CXCR1/2 signaling pathway also plays an important role in tumor progression (Ha H et al. 2017). For example, CXCL8 induces cell proliferation and angiogenesis via both receptors in melanoma cell lines. Thereby, CXCR2 plays an important role in regulating CXCL8-mediated invasive and migratory behavior of human melanoma cells. Therefore, blockade of the CXCL8 signaling axis holds promise for the treatment of cancer and metastatic melanoma in particular. (Gabellini C et al. 2009).

1. Gabellini C et al. (2009) Functional activity of CXCL8 receptors, CXCR1 and CXCR2, on human malignant melanoma progression. Eur J Cancer 45:2618-2627
2. Ha H et al. (2017) Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases. Theranostics. 7):1543-1588.
3. Liu Q et al. (2016) The CXCL8-CXCR1/2 pathways in cancer. Cytokine Growth Factor Rev 31:61-71.