TAZ^Q233del Hijacks Hippo pathway to promote mesenchymal-epithelial transition in pancreatic adenocarcinoma cells

The Hippo pathway is crucial in organ size control, and its dysregulation contributes to tumorigenesis. TAZ is an essential molecule containing a WW domain in Hippo pathway and serves as transcription co-activator to modulate cell proliferation and induce epithelial-mesenchymal transition in different human cancers, including pancreatic adenocarcinoma. In this study, we found that TAZ^Q233del, a deletion occurred at its transactivation domain, increases phosphorylation at TAZ Ser89, resulting in sequestration of TAZ in cytoplasm and inhibiting its transcriptional activity. Furthermore, ectopic expression of TAZ^Q233del promotes mesenchymal-epithelial transition (MET), demonstrating that Q233 is an essential site to control TAZ function. Our results disclose that TAZ^Q233del plays a major role in regulating malignancy of cancer cells by hijacking Hippo pathway.