Abstract B06: Complex requirement of YAP and TAZ in gastrointestinal development and tumorigenesis

YAP and TAZ are the major intracellular mediators of Hippo signaling in mammals; however, the precise function of YAP/TAZ in gastrointestinal development and tumorigenesis remains poorly understood. By specific removal of YAP/TAZ from the developing endoderm and gastrointestinal tract, we find that YAP/TAZ are dispensable for Wnt signal transduction and normal gastrointestinal epithelial differentiation, but act as the direct TCF4 targets and downstream effectors during epithelial transformation. Surprisingly, our loss- and gain-of-function genetic analyses identify an essential role for YAP/TAZ in the gastrointestinal mesenchyme as a molecular switch to coordinate growth and differentiation. We find that YAP/TAZ are required for the expansion of the primitive progenitor populations critical for mesenchymal growth. However, persistent YAP activation inhibits the induction of the smooth muscle lineage, and YAP/TAZ down-regulation during later development is essential for Hedgehog signaling-induced differentiation of smooth muscle cells. Taken together, our studies uncover a complex requirement of YAP/TAZ in the gastrointestinal tract and demonstrate the functional interplays among key signaling pathways during gastrointestinal development and tumorigenesis.Citation Format: Jennifer L. Cotton, Qi Li, Lifang Ma, Tony Ip, Randy Johnson, Junhao Mao. Complex requirement of YAP and TAZ in gastrointestinal development and tumorigenesis. [abstract]. In: Proceedings of the AACR Special...

Source: Molecular Cancer Research - May 2, 2016 Category: Cancer & Oncology Authors: Cotton, J. L., Li, Q., Ma, L., Ip, T., Johnson, R., Mao, J. Tags: Signaling Pathways: Hippo/TOR: Poster Presentations - Proffered Abstracts Source Type: research