TGFB1 and familial pancreatic carcinoma: Based on these findings, we hypothesize that the hypoxic microenvironment in pancreatic cancer activates the TGF-β1/Smad signaling pathway via HIF-1α, thereby synergistically promoting the expression of ECM proteins (e.g., collagen I/III/V) and exacerbating tumor invasion and stromal fibrosis.