This novel finding was validated by driving role that the functional CAF-induced IL-33 plays in cancer cells, to regulate CXCR4 expression, wherein the autocrine cancer-secreting IL-33 automatically target the surface receptor ST2 and, subsequently, enhance the IL-33/ST2 signaling cascade transcriptional upregulation of CXCR4, which then generates the newly discovered “IL-33/CXCR4 regulatory circuit,” which undergoes repeated amplification for further activation of the SDF-1/CXCR4 signaling transduction. The gene discussed is IL33; the disease is cancer.