Project description:Yes-associated protein 1 (YAP1) is an effector of Hippo pathway, which is critical for regulating organ size, cell proliferation and tumor growth in mammals. YAP1 is known to be involved in tumorigenesis in several tissues, yet its role in colorectal cancer(CRC) is not established. To investigate the effect of YAP1 in CRC, we used microarrays to compared human colon cancer cell line HCT116 transfected with a control non-targeting siRNA to cells and transfected with siRNA targeting YAP1.
Project description:The "Cell Painting Assay", an image profile-based drug-discovery platform, identified NB4A as a putative small molecule inhibitor of Yes-associated protein 1 (Yap1). Treatment of KP230 cells with 10 µm NB4A daily for 3 days reduced Yap1 protein levels. Thus, we used RNA sequencing to investigate NB4A-mediated global gene expression changes in these cells.
Project description:The Hippo pathway effector YAP1 controls stem cell fate in epithelial tissues, but its role in stem cells of non-epithelial tissues, such as skeletal muscle, is poorly documented. Here we show that sustained YAP1 activity in mouse activated satellite cells in vivo induces rhabdomyosarcoma (RMS) resembling human embryonal RMS (ERMS) with high penetrance and short latency. The transcriptional program of YAP1 in ERMS drives pro-proliferative pathways whilst decreasing MyoD1 and MEF2 pro-differentiation activity to globally maintain the myoblastic phenotype of ERMS. Normalization of YAP1 expression reduced tumor burden and allowed myogenic differentiation of YAP1-driven and RD ERMS xenografts in situ, thereby identifying YAP1 as a potent RMS-causing oncogene and potential target for differentiation therapy. A total of four samples were analyzed. Two ChIP-Seq datasets from RD human cells, containing reads connected to TEAD binding and IgG binding as control/background; two ChIP-Seq datasets from YAP-ERMS mouse cells, containing reads connected to TEAD binding and Input reads as control/background
