ROBO2 is a stroma suppressor gene in the pancreas and acts via TGF-β signalling.

ABSTRACT: Whereas genomic aberrations in the SLIT-ROBO pathway are frequent in pancreatic ductal adenocarcinoma (PDAC), their function in the pancreas is unclear. Here we report that in pancreatitis and PDAC mouse models, epithelial Robo2 expression is lost while Robo1 expression becomes most prominent in the stroma. Cell cultures of mice with loss of epithelial Robo2 (Pdx1^Cre;Robo2^F/F) show increased activation of Robo1⁺ myofibroblasts and induction of TGF-β and Wnt pathways. During pancreatitis, Pdx1^Cre;Robo2^F/F mice present enhanced myofibroblast activation, collagen crosslinking, T-cell infiltration and tumorigenic immune markers. The TGF-β inhibitor galunisertib suppresses these effects. In PDAC patients, ROBO2 expression is overall low whi

SUBMITTER: Pinho AV 

PROVIDER: S-EPMC6269509 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature