Key factors secreted by CAFs—including HGF, IL-6, folliculostatin-like protein 1 (FSTL1), and cardiotropic cytokine-like factor 1 (CLCF1)—activate multiple signaling pathways such as MET-ERK1/2, STAT3/Notch, TLR4/AKT/mTOR, and CLCF1/CXCL6-TGF-β autocrine circuits (54, 55), collectively promoting stemness marker expression and tumor stem cell self-renewal. Here, AKT1 is linked to neoplasm.