TEAD mediates YAP-dependent gene induction and growth control

TLDR

The YAP transcription coactivator is an oncogene amplified in human cancers and is regulated by phosphorylation through the Hippo tumor suppressor pathway. The study aims to determine whether TEAD transcription factors are essential mediators of YAP-dependent gene expression. The authors demonstrate that TEAD family transcription factors mediate YAP-driven transcription. TEAD is required for YAP-induced cell growth, oncogenic transformation, and epithelial‑mesenchymal transition, with CTGF identified as a direct YAP target, and this functional relationship is conserved in Drosophila, establishing TEAD as a new essential component of the Hippo pathway.

Abstract

The YAP transcription coactivator has been implicated as an oncogene and is amplified in human cancers. Recent studies have established that YAP is phosphorylated and inhibited by the Hippo tumor suppressor pathway. Here we demonstrate that the TEAD family transcription factors are essential in mediating YAP-dependent gene expression. TEAD is also required for YAP-induced cell growth, oncogenic transformation, and epithelial-mesenchymal transition. CTGF is identified as a direct YAP target gene important for cell growth. Moreover, the functional relationship between YAP and TEAD is conserved in Drosophila Yki (the YAP homolog) and Scalloped (the TEAD homolog). Our study reveals TEAD as a new component in the Hippo pathway playing essential roles in mediating biological functions of YAP.