The Prolyl Isomerase PIN1 Affects Fibroblast Differentiation States and Cross-talk in Pancreatic Cancer.

ABSTRACT: The prolyl isomerase PIN1 is overexpressed in cancer and contributes to cancer cell-intrinsic phenotypes, including proliferation and migration. However, PIN1 may also function in stromal cells within the tumor microenvironment. In this study, we showed that PIN1 is a critical regulator of pancreatic stellate cell (PSC) state at baseline and in response to the myofibroblast-activating factor TGFβ. Loss or inhibition of PIN1 altered the epigenetic and transcriptional responses of PSCs to TGFβ, preventing PSC differentiation to a myofibroblast state and altering expression of secreted matrix proteins and signaling molecules. Consistent with inhibition of the TGFβ response, low fibroblast PIN1 expression in mouse and human pancreatic ductal adenocarcinoma correlated with low expression of αSM

SUBMITTER: Bowman CL 

PROVIDER: S-EPMC12912258 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature