Tumor-derived factors such as TGF-β, PDGF, and IL-6 trigger the activation of CAFs, endowing them with pro-tumorigenic functions. CAFs are highly heterogeneous and influence tumor progression through multiple interconnected mechanisms—including secretion of cytokines, remodeling of ECM, immune modulation, and metabolic reprogramming. This evidence concerns the gene TGFB1 and neoplasm.