Regulation of the Hippo pathway by phosphoinositol transfer protein (PITP) and phosphoinositides

ABSTRACT: The Hippo pathway plays a key role in development, organ size control, and tissue homeostasis, and its dysregulation contributes to cancer. The LATS tumor suppressor kinases phosphorylate and inhibit the YAP/TAZ transcriptional co-activators to suppress gene expression and cell growth. Through a screen of marine natural products, we identified microcolin B (MCB) as a Hippo activator. Structure-activity optimization yielded more potent MCB analogs, which led to identification of PITP as the direct molecular targets. We established a critical role of PITP in regulating LATS and YAP. Moreover, we showed that PITP influences the Hippo pathway via cellular PI4P. This study uncovers a previously unrecognized role of PITP in Hippo pathway regulation and as potential cancer therapeutic targets.

ORGANISM(S): Homo sapiens

PROVIDER: GSE198890 | GEO | 2022/03/20

REPOSITORIES: GEO