Functions of YAP/TAZ in pituitary tumours (360G-Wellcome-211841_Z_18_Z)

This proposal will explore how activation and accumulation of YAP and TAZ, effectors of the Hippo pathway, influence the fate and behaviour of pituitary tumour cells in vitro. Our data indicate that YAP/TAZ accumulation represses the activity of the growth hormone and prolactin promoters in mammosomatotropinoma GH3 cells, a rat pituitary tumour-derived cell line. By carrying out siRNA-mediated knockdown of Lats1, which normally inactivates YAP/TAZ, we will assess if, concomitant with a repression of differentiation, there is an increase of pituitary progenitor/stem cell markers. This will reveal if YAP/TAZ act to promote the uncommitted progenitor/stem state. In addition, we will determine if accumulation of YAP/TAZ leads to changes in cell cycle length, the number of proliferating cells and in migration behaviour. These findings will be relevant to our understanding of the function of YAP/TAZ in pituitary tumours as well as normal pituitary development and homeostasis, and will complement our in vivo research in mouse models and human pituitary tumours.