Further, sEcad induced reactive astrocytosis through the CXCL1/CXCL8-CXCR2 axis, and treatment with a brain-permeable CXCR2 antagonist reduced metastatic burden and prolonged survival in the brain metastasis models.<h4>Conclusion</h4>sEcad drives brain metastasis by promoting invasion and anoikis resistance in cancer cells and inducing an inflammatory brain microenvironment via a targetable CXCL1/CXCL8-CXCR2 axis. This evidence concerns the gene CXCR2 and cancer.