ACKR3-overexpressing tumor cells secrete EVs containing miR146a-5p and miR155-5p. These microRNAs are endocytosed by cancer-associated fibroblasts which get activated via JAK2-STAT3/NF-B-dependent signaling. Subsequently, these fibroblasts secrete inflammatory cytokines, including CXCL12. CXCL12 activates ACKR3 on the tumor cells, inducing EMT and pre-metastatic niche formation. The gene discussed is CXCL12; the disease is cancer.