{"doi":"10.7554/elife.98386","title":"VGLL2 and TEAD1 fusion proteins identified in human sarcoma drive YAP/TAZ-independent tumorigenesis by engaging EP300","abstract":"Studies on Hippo pathway regulation of tumorigenesis largely center on YAP and TAZ, the transcriptional co-regulators of TEADs. Here, we present an oncogenic mechanism involving VGLL and TEAD fusions that is Hippo pathway-related but YAP/TAZ-independent. We characterize two recurrent fusions, VGLL2-NCOA2 and TEAD1-NCOA2 , recently identified in human spindle cell rhabdomyosarcoma. We demonstrate that in contrast to VGLL2 and TEAD1 the fusion proteins are potent activators of TEAD-dependent transcription, and the function of these fusion proteins does not require YAP/TAZ. Furthermore, we identify that VGLL2 and TEAD1 fusions engage specific epigenetic regulation by recruiting histone acetyltransferase EP300 to control TEAD-mediated transcriptional and epigenetic landscapes. We show that small-molecule EP300 inhibition can suppress fusion protein-induced oncogenic transformation both in vitro and in vivo in mouse models. Overall, our study reveals a molecular basis for VGLL involvement in cancer and provides a framework for targeting tumors carrying VGLL , TEAD , or NCOA translocations.","journal":"eLife","year":2024,"id":484901,"datarank":0.42064939833455983,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.10873316708258438,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.10873316708258438,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":7,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9621,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE260781","GSE260782","GSE260783"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":640710,"name":"Xiaodi Hu","orcid":"0000-0001-9704-2474","position":1,"is_corresponding":false},{"id":246159,"name":"Jennifer L. Cotton","orcid":"0000-0003-0106-1801","position":2,"is_corresponding":false},{"id":248486,"name":"Lifang Ma","orcid":null,"position":3,"is_corresponding":false},{"id":246155,"name":"Qi Li","orcid":"0000-0001-7786-6839","position":4,"is_corresponding":false},{"id":1327043,"name":"Jiangtao Cui","orcid":"0009-0008-9935-5261","position":5,"is_corresponding":false},{"id":1327044,"name":"Yongjie Wang","orcid":"0000-0003-4870-2805","position":6,"is_corresponding":false},{"id":762369,"name":"Ritesh Thakare","orcid":"0000-0002-7426-2519","position":7,"is_corresponding":false},{"id":735859,"name":"Zhipeng Tao","orcid":"0000-0002-9582-6950","position":8,"is_corresponding":false},{"id":246166,"name":"Y. Tony Ip","orcid":"0000-0003-4370-7906","position":9,"is_corresponding":false},{"id":246169,"name":"Xu Wu","orcid":"0000-0002-1624-0143","position":10,"is_corresponding":false},{"id":869569,"name":"Jiayi Wang","orcid":"0000-0003-1688-2864","position":11,"is_corresponding":false},{"id":246170,"name":"Junhao Mao","orcid":"0000-0003-1980-1177","position":12,"is_corresponding":false},{"id":1327042,"name":"Susu Guo","orcid":"0000-0002-7481-6884","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T02:07:42.971417Z","pmid":"40338073","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}