Another major axis is CXCL12/CXCR4, where stromal-derived CXCL12 engages CXCR4 on CSCs to facilitate migration, niche homing, and dormancy, especially in breast and pancreatic cancers.247 TGF-β, which is largely produced by CAFs and immune cells, induces SMAD-mediated transcriptional programs that drive CSC plasticity and EMT and is known to enrich CSC populations in hepatocellular carcinoma.106. This evidence concerns the gene TGFB1 and hepatocellular carcinoma.