Project description:Purpose: The goal of this study is to understand the signaling pathway alteration in NCI-H226 cells treated with new TEAD autopalmitoylation inhibitor TM2, and to further validate TEAD inhibitor for specifity in TEAD-YAP interuption. Methods: Mesothelioma cell line NCI-H226 was chosen to be treated with TEAD palmitoylation inhibitor TM2 at 1μM for 24 hours. Total RNA was isolated for the analysis. RNA samples were sent to Novogen for library construction, RNA sequencing and raw data process. Conclusions: Our study privides gene expression profiling evidence to validate our TEAD palmitoylation inhibitor TM2 as specific small molecule to block TEAD transcriptional activity in mesothelioma cells.
Project description:Purpose: The goal of this study is to understand the signaling pathway alteration in NCI-H226 cells treated with TEAD inhibitors. Methods: Mesothelioma cell line NCI-H226 was chosen to be treated with TEAD inhibitors at 1μM for 24 hours. Total RNA was isolated for the analysis. RNA samples were sent to Novogen for library construction, RNA sequencing and raw data process. Conclusions: Our study privides gene expression profiling evidence to validate TEAD inhibitors to block TEAD transcriptional activity in mesothelioma cells.
Project description:We investigate the dependence of human malignant mesothelioma on functional TEAD transcription factors to maintain fully established tumors in vivo. We show that TEAD inhibitor K-975 stops tumor growth in vivo, eventually causing tumor regression, by downregulating TEAD activity and altering, thus, TEAD-dependent transcription in a dysfunctional Hippo genetic background. Our data validate the concept of inhibiting an activated YAP1/TEAD complex for the treatment of malignant pleural mesothelioma patients.
Project description:The goal of this experiment is to identify changes in TEAD1 protein interactions upon treatment with TEAD small molecule inhibitors. NCI-H226 cells were treated for 24h with DMSO vehicle control or a TEAD inhibitor, GNE-7883 or Compound 2. Immunoprecipitation of TEAD1 was performed and the resulting protein samples were processed for tandem mass tag (TMT) labeling and quantitative proteomic analysis. Pooled TMT-labeled samples were fractionated into six fractions and the experiment was performed in triplicate. For further experimental details, see the Materials and Methods section in the manuscript.
Project description:The goal of this experiment is to identify changes in TEAD4 protein interactions upon treatment with TEAD small molecule inhibitors. NCI-H226 cells were treated for 24h with DMSO vehicle control or a TEAD inhibitor, GNE-7883 or Compound 2. Immunoprecipitation of TEAD4 was performed and the resulting protein samples were processed for tandem mass tag (TMT) labeling and quantitative proteomic analysis. Pooled TMT-labeled samples were fractionated into six fractions and the experiment was performed in triplicate. For further experimental details, see the Materials and Methods section in the manuscript.
