C-X-C motif chemokine receptor 1 (CXCR1) and ligands CXCL5/CXCL6 (CXCL5/6-CXCR1 axis)

The CXCL5/6-CXCR1 axis is a critical signaling pathway involved in the recruitment and activation of neutrophils and the regulation of the tumor microenvironment. CXCR1 is a G protein-coupled receptor that primarily binds CXCL8 (IL-8) and CXCL6 with high affinity, while CXCL5 and CXCL6 are pro-inflammatory chemokines that promote chemotaxis and angiogenesis. In many cancers, this axis is upregulated, driving tumor progression, epithelial-mesenchymal transition (EMT), and the maintenance of cancer stem cells, particularly in breast and pancreatic malignancies. Beyond oncology, the axis plays a significant role in chronic inflammatory diseases like COPD and ulcerative colitis by mediating excessive neutrophil infiltration and tissue damage. Therapeutic strategies targeting this axis typically involve small molecule inhibitors like Reparixin, which aim to block the receptor's activity to reduce inflammation and inhibit metastatic spread. (Sources: UniProt P25024; PubMed: 29109418, 22490440; NIH/NCBI Gene ID: 3577).

Other names

CXCR1Interleukin 8 receptor alphaIL8RACD181CXCL5 (Epithelial-derived neutrophil-activating peptide 78)ENA-78CXCL6 (Granulocyte chemotactic protein 2)GCP-2

Allosteric inhibition or competitive antagonism of the CXCR1 and/or CXCR2 receptors to prevent ligand binding and downstream signaling, thereby reducing neutrophil infiltration and inhibiting tumor cell proliferation and metastasis.