Figure 2. Effects of cardinal genomic alterations in PDA may disparately influence fibroblast context, function and heterogeneity.

Activating Kras mutation in pancreatic epithelial cells induces production of Il-6 and Shh, which help convert quiescent PSC to activated fibroblasts. Subsequent mutation of Trp53, loss of Smad4 and/or silencing of Cdkn2a in the neoplastic epithelium may differentially shape the ECM through distinct mechanisms of paracrine signaling to fibroblasts.