{"database":"GEO","file_versions":[],"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=GSE311396"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"NELFA-mediated promoter-proximal pausing restrains YAP-driven transcription and shapes context-dependent outcomes in breast cancer","description":"Overexpression of YAP is associated with oncogenesis and tumor progression in multiple malignancies. YAP is the key transcriptional effector of a highly conserved Hippo signaling pathway, from Drosophila (Yki) to humans (YAP). In our previous Drosophila screen, we identified NELFA, a core component of the promoter-proximal pausing (PPP) complex, as a suppressor of Yki-driven hyperproliferation. Building on this observation, we investigated whether this PPP–YAP regulatory interaction is conserved in mammalian cells, using breast cancer as a model system. Using HEK293T and MDA-MB-231 cells, we demonstrate that NELFA depletion selectively amplifies YAP-driven transcription, thereby enhancing the expression of canonical YAP target genes. Whole-transcriptome analysis of NELFA-depleted MDA-MB-231 cells revealed widespread reprogramming upon NELFA loss, with strong enrichment of conserved YAP signatures, EMT and TGF-β pathways, and AP-1/TEAD-SMAD3 transcriptional networks—indicating that NELFA regulates a broad YAP-centered oncogenic module. Clinical analysis of an Indian breast cancer cohort and TCGA revealed a striking context-dependent role for NELFA. Low NELFA expression predicted poor disease-free survival in YAP-high tumors—particularly in triple-negative breast cancer (TNBC)—suggesting a tumor-suppressive role. While High NELFA expression correlated with poorer overall survival. Collectively, these findings reveal that NELFA’s role in YAP-driven transcription is context-dependent in the breast cancer setting.","dates":{"publication":"2026/05/15"},"accession":"GSE311396","cross_references":{"GSM":["GSM9324449","GSM9324445","GSM9324456","GSM9324446","GSM9324447","GSM9324448","GSM9324452","GSM9324453","GSM9324454","GSM9324455","GSM9324450","GSM9324451"],"GPL":["34284"],"GSE":["311396"],"taxon":["Homo sapiens"],"PMID":["[42100387]"]}}