{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE302nnn/GSE302321/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302321"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Co-targeting EZH2 and TEAD elicits apoptosis through tumor-intrinsic innate immune signaling in Hippo pathway-mutated cancers - ChIP-seq data from genetic disruption of EZH2","description":"TEA/TEF-domain [TEAD] inhibitors are being evaluated in clinical trials for cancers with alterations in the Hippo pathway including mesothelioma. We recently developed and showcased the potency of TEAD palmitoylation inhibitors MYF-03-69 and MYF-03-176 in mesothelioma cell lines. However, TEAD inhibition results in cell cycle arrest in cell line models with Hippo pathway alterations without inducing cell death, potentially limiting their long-term clinical efficacy. Using a genome-wide CRISPR/Cas9 screen, we identified EZH2 as a critical modulator of the cellular response to TEAD inhibition. Compared to single agent treatments, EZH2i/TEADi robustly triggered apoptosis and suppressed the growth of Hippo-mutated cells in vitro and in vivo. Mechanistically, EZH2i/TEADi-treated cells exhibited heightened activation of tumor-intrinsic innate immune signaling which resulted in DNA damage and subsequent apoptosis. Taken together, we propose this novel combinatorial strategy as a potential approach to enhancing the anti-tumor efficacy of single agent TEAD targeting therapies in Hippo pathway altered tumors. This GEO accession includes the data series associated with ChIP-seq derived from genetic disruption of EZH2.","dates":{"publication":"2026/07/17"},"accession":"GSE302321","cross_references":{"GSM":["GSM9101839","GSM9101836","GSM9101858","GSM9101857","GSM9101835","GSM9101838","GSM9101859","GSM9101837","GSM9101843","GSM9101865","GSM9101864","GSM9101842","GSM9101867","GSM9101845","GSM9101866","GSM9101844","GSM9101861","GSM9101860","GSM9101863","GSM9101841","GSM9101840","GSM9101862","GSM9101829","GSM9101828","GSM9101847","GSM9101846","GSM9101868","GSM9101849","GSM9101848","GSM9101832","GSM9101854","GSM9101831","GSM9101853","GSM9101856","GSM9101834","GSM9101833","GSM9101855","GSM9101850","GSM9101852","GSM9101830","GSM9101851"],"GPL":["24676"],"GSE":["302321"],"taxon":["Homo sapiens"]}}