WWTR1(TAZ)-CAMTA1 reprograms endothelial cells to drive epithelioid hemangioendothelioma

Jordan H. Driskill, Yonggang Zheng, Bo Kuan Wu, Li Wang, Jing Cai, Dinesh Rakheja, Michael Dellinger, Duojia Pan

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)495-511
Number of pages17
JournalGenes and Development
Issue number7
StatePublished - Apr 1 2021


  • CAMTA1
  • Cancer
  • Endothelial cells]
  • Epithelioid hemangioendothelioma
  • Gene fusion
  • Hippo pathway
  • TAZ
  • Vascular anomalies
  • Vascular malformations
  • YAP

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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