Over the past nearly four decades, TGF-β has been further explored and found to be widely produced by nearly all cell types including CAFs, and the TGF-β signaling pathway has been found to have pleiotropic effects on CAF behaviors through autocrine and paracrine mechanisms.15,38,84 Resident NFs can be induced to transition into CAFs by TGF-β1 in various tumors, including bladder, breast, colorectal, and pancreatic cancer,38,85,86 indicating that TGF-β1-driven CAF generation is a common event during cancer development. This evidence concerns the gene TGFB1 and familial pancreatic carcinoma.