By developing patient-derived models to dissect the microenvironmental interaction between CAFs and tumor cells, we also described CAF-secreted TGF-β2, a member of the TGF-β family, inducing the expression of GLI Family Zinc Finger 2 (GLI2), an important effector of Hedgehog signaling, as a predominant pathway to promote CRC stemness and chemoresistance [20] (Fig. 1). The gene discussed is TGFB1; the disease is colorectal carcinoma.