As one biological readout for how PDAC cells respond to CAFs, we considered the ability of CAF-produced ECM to upregulate tumor cell expression of CTGF, a YAP target gene and matricellular protein produced by both stromal and tumor cells that mediates their cross-talk, promotes fibrosis, and enhances tumor initiation in pancreatic cancer (35, 36). This evidence concerns the gene CCN2 and familial pancreatic carcinoma.