Indeed, the effect of autocrine TGF-β signaling on CAFs remained unclear until a study demonstrated that the establishment of TGF-β autocrine signaling pathways induced CAF formation during breast cancer progression,108 indicating that tumor-derived TGF-β, in a positive-feedback loop, could affect the biological characteristics of CAFs and that the crosstalk between CAFs and cancer cells is not unidirectional but bidirectional (Fig. 2). The gene discussed is TGFB1; the disease is cancer.