GSE118765
TGF-ß and RREB1 coordinate EMT programs in development and cancer
Epithelial-to-mesenchymal transitions (EMT) play prominent roles during development, regeneration and tumor progression. EMTs are triggered by TGF-ß, RAS and other signals that cooperatively induce the expression of master EMT transcription factors such as SNAIL. Here, we elucidate how the TGF-ß and RAS pathways jointly trigger EMTs and tie them to broader developmental programs. We identify RAS response element binding protein 1 (RREB1) as a critical partner of TGF-ß-activated SMAD transcription factors in driving SNAIL expression in pancreatic pre-malignant epithelial cells, lung adenocarcinoma cells, and embryonic stem cells. Moreover, SMADs and RREB1 also drive EMT-associated fibrogenic programs in epithelial cells and mesendoderm differentiation in pluripotent embryonic cells. These findings illuminate the orchestration of EMT associated programs in gastrulation, fibrosis, and cancer. Overall design: RNA-seq, ChIP-seq, and ATAC-seq are used to profile pancreatic organoid, pancreatic adenocarcinoma cells, and embryonic stem cells