It has been reported that upon induction by CRC cell-derived soluble factors, the TGF-β signaling is activated in CAFs, accompanied by increased expression of TGF-β itself, suggesting a cumulative production of TGF-β within the TME that promotes the transdifferentiation of resident fibroblasts into CAFs (Hawinkels et al., 2014). This evidence concerns the gene TGFB1 and colorectal carcinoma.