{"doi":"10.1101/gad.348221.120","title":"WWTR1(TAZ)-CAMTA1 reprograms endothelial cells to drive epithelioid hemangioendothelioma","abstract":"Epithelioid hemangioendothelioma (EHE) is a poorly understood and devastating vascular cancer. Sequencing of EHE has revealed a unique gene fusion between the Hippo pathway nuclear effector TAZ (WWTR1) and the brain-enriched transcription factor CAMTA1 in ∼90% of cases. However, it remains unclear whether the TAZ-CAMTA1 gene fusion is a driver of EHE, and potential targeted therapies are unknown. Here, we show that TAZ-CAMTA1 expression in endothelial cells is sufficient to drive the formation of vascular tumors with the distinctive features of EHE, and inhibition of TAZ-CAMTA1 results in the regression of these vascular tumors. We further show that activated TAZ resembles TAZ-CAMTA1 in driving the formation of EHE-like vascular tumors, suggesting that constitutive activation of TAZ underlies the pathological features of EHE. We show that TAZ-CAMTA1 initiates an angiogenic and regenerative-like transcriptional program in endothelial cells, and disruption of the TAZ-CAMTA1-TEAD interaction or ectopic expression of a dominant negative TEAD in vivo inhibits TAZ-CAMTA1-mediated transformation. Our study provides the first genetic model of a TAZ fusion oncoprotein driving its associated human cancer, pinpointing TAZ-CAMTA1 as the key driver and a valid therapeutic target of EHE.","journal":"Genes & Development","year":2021,"id":212913,"datarank":1.8870916880477224,"base_score":4.110873864173311,"endowment":4.110873864173311,"self_citation_contribution":0.6166310796259968,"citation_network_contribution":1.2704606084217256,"self_endowment_contribution":0.6166310796259968,"citer_contribution":1.2704606084217256,"corpus_percentile":null,"corpus_rank":null,"citation_count":60,"citer_count":57,"citers_with_citation_signal":46,"citers_with_endowment":46,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":804097,"name":"Yonggang Zheng","orcid":"0000-0002-3326-4614","position":1,"is_corresponding":false},{"id":804811,"name":"Bo-Kuan Wu","orcid":null,"position":2,"is_corresponding":false},{"id":804098,"name":"Li Wang","orcid":"0000-0001-8041-7188","position":3,"is_corresponding":false},{"id":804099,"name":"Jing Cai","orcid":"0000-0003-4128-572X","position":4,"is_corresponding":false},{"id":376335,"name":"Dinesh Rakheja","orcid":"0000-0001-6888-7902","position":5,"is_corresponding":false},{"id":480470,"name":"Michael T. Dellinger","orcid":"0000-0002-3315-4239","position":6,"is_corresponding":false},{"id":334176,"name":"Duojia Pan","orcid":"0000-0003-2890-4645","position":7,"is_corresponding":false},{"id":804096,"name":"Jordan H. Driskill","orcid":"0000-0003-4319-3845","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:52:31.378994Z","pmid":"33766984","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":[]}