The uptake of HSPC111 by hepatic stellate cells causes their reprogramming into cancer-associated fibroblasts (CAFs) and the expression and secretion of CCL5, which further sustains exosomal HSPC111 excretion from cancer cells; thus, it creates a positive feedback loop and triggers EMT of colon cancer cells in vitro and experimental metastasis in vivo. This evidence concerns the gene NOP16 and malignant colon neoplasm.