The IL-8–Regulated Chemokine Receptor CXCR7 Stimulates EGFR Signaling to Promote Prostate Cancer Growth

摘要: The pro-inflammatory chemokine receptor CXCR7 that binds the ligands CXCL11 and CXCL12 (SDF-1a) is elevated in a variety of human cancers, but its functions are not understood as it does elicit classical signaling. Here we report pro-cancerous cytokine IL-8 up regulates expression along with ligand-independent promote growth proliferation prostate cancer cells (CaP cells). In cell culture, ectopic or addition selectively increased at level mRNA protein production. Conversely, suppressing signaling abolished ability to regulate CXCR7. RNAi-mediated knockdown CaP caused multiple anti-tumor effects, including decreased proliferation, cycle arrest G1 phase, proteins involved S phase progression. contrast, ligand SDF-1a did affect proliferation. Over normal their manner associated levels phospho-EGFR (pY1110) phospho-ERK1/2. Notably, co-immunoprecipitation studies established physical association EGFR, linking CXCR7-mediated EGFR activation. Consistent these findings, CXCR7-depleted tumors grew more slowly than control tumors, expressing tumor VEGF, cyclin D1 p-EGFR. Together, results reveal novel mechanism promotion by co-regulation factor cancer.