{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE253nnn/GSE253631/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE253631"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Loss of FAM60A disrupts Sin3/HDAC control of the Hippo signaling and promotes oncogenic YAP1 activation","description":"FAM60A (also known as SINHCAF) is a subunit of the Sin3/HDAC histone deacetylase complex with established roles in chromatin remodeling, yet its broader cellular functions remain largely undefined. Using immunological, biochemical, CRISPR/Cas9, genomic, and proteomic approaches, we mapped the FAM60A interaction network and its functional impact. We reveal that FAM60A binds directly to HDAC1 to recruit Sin3/HDAC to SIN3A, while a dual domain architecture mediates additional associations with RNA and DNA binding proteins. CRISPR/Cas9–mediated HDAC1 knockout abolishes the FAM60A–SIN3A interaction, confirming this dependency. Loss of FAM60A triggers widespread transcriptional rewiring, including downregulation of WWC3—a scaffold for LATS1/2 activation. Consequently, YAP1 dephosphorylation and nuclear accumulation shifted cell-cycle dynamics toward G₁ enrichment and conferred resistance to metabolic stress. Restoration of FAM60A or exogenous WWC3 reactivated Hippo “off” signaling, normalized cell-cycle distribution, and reversed stress resistance. These findings establish FAM60A as a pivotal epigenetic tuner linking histone deacetylation to Hippo pathway regulation and nominate the FAM60A–HDAC1–WWC3 axis as a potential therapeutic target to restore growth control in YAP-driven cancers.","dates":{"publication":"2026/04/30"},"accession":"GSE253631","cross_references":{"GSM":["GSM8024387","GSM8024392","GSM8024391","GSM8024390","GSM8024389","GSM8024388"],"GPL":["21697"],"GSE":["253631"],"taxon":["Homo sapiens"]}}