Central role of Yes-associated protein and WW-domain-containing transcriptional co-activator with PDZ-binding motif in pancreatic cancer development

Figure 1 Yes-associated protein and WW-domain-containing transcriptional co-activator with PDZ-binding motif is a point of convergence in signaling pathways. A network that involves activated Ras, G protein-coupled receptors (GPCRs) and tyrosine kinase receptors positively regulates Yes-associated protein and WW-domain-containing transcriptional co-activator with PDZ-binding motif (YAP/TAZ) activity via Rho/PKD/organization of the actin cytoskeleton and PI3K/AKT/mTORC1. The interaction of mTORC1 and YAP is explained in the text. In addition, the localization and activity of YAP/TAZ is negatively impacted by the Hippo pathway which mediates phosphorylation of YAP and thereby its cytoplasmic sequestration. Metformin and statins inhibit YAP/TAZ activity at different sites in the network. Stimulatory effects are shown by black arrows whereas inhibitory effects are indicated by red arrows. YAP/TAZ: Yes-associated protein and WW-domain-containing transcriptional co-activator with PDZ-binding motif; GPCR: G protein-coupled receptor.

Figure 2 Schematic overview of the mevalonate pathway. The scheme illustrates the site of action of statins, metformin and bromodomain and extra-terminal domain inhibitors (see text for details). BET: Bromodomain and extra-terminal domain; AMPK: AMP-activated protein kinase; GG-PP: Geranylgeranyl pyrophosphate.