Figure 2.

Effects of TGFβ depending of pancreatic ductal adenocarcinoma stages. At early stages, TGFβ acts as a tumor suppressor, by promoting cell-cycle arrest through repression of c-Myc expression and cyclin-dependent kinase (CDK), and through enhancement of CDK inhibitor (CDKI) expression, thereby enhancing apoptosis and stimulating differentiation of precursor cells into a less proliferative stage. At late stages, TGFβ acts as a tumor promoter through immune evasion by stimulation of regulatory T cells and by inhibition of natural killers (NKs), macrophages, T cells, and dendritic cells (DCs). TFGβ acts also on the microenvironment by promoting desmoplasia and angiogenesis, and it triggers epithelial-to-mesenchymal transition (EMT) through induction of expression of transcription factors Snail and Zeb1/2.