Hippo signalling pathway mediates oncogenic properties of NAB2::STAT6 in solitary fibrous tumour
Purpose: Solitary fibrous tumour (SFT) is a rare mesenchymal neoplasm molecularly defined by the NAB2::STAT6 gene fusion (GF), an aberrant transcriptional regulator whose functions beyond EGR1 activation remain incompletely understood. This study aimed to further elucidate the oncogenic role of NAB2...
| Autores: | , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2026 |
| País: | España |
| Institución: | Universidad de Cantabria (UC) |
| Repositorio: | UCrea Repositorio Abierto de la Universidad de Cantabria |
| Idioma: | inglés |
| OAI Identifier: | oai:dnet:ucreareposit::2e4bc25105cd6c9f2be6f562a8072119 |
| Acceso en línea: | https://hdl.handle.net/10902/40039 |
| Access Level: | acceso abierto |
| Palabra clave: | Solitary fibrous tumour Gene fusion NAB2:STAT6 Hippo signalling pathway Dasatinib |
| Sumario: | Purpose: Solitary fibrous tumour (SFT) is a rare mesenchymal neoplasm molecularly defined by the NAB2::STAT6 gene fusion (GF), an aberrant transcriptional regulator whose functions beyond EGR1 activation remain incompletely understood. This study aimed to further elucidate the oncogenic role of NAB2::STAT6 and to identify potential therapeutic vulnerabilities. Methods: Human mesenchymal stem cell-derived SFT models (SFT-MSCs) were generated via ectopic expression of NAB2::STAT6 and analysed by gene expression microarray to assess the impact of this fusion on the transcriptomic profile. Stable SFT-MSC clones were subjected to functional assays following YAP1/TAZ silencing via siRNAs or pharmacological inhibition with dasatinib. Transcriptomic profiling of 16 tumours was performed to investigate correlations between Hippo pathway and EGR1 transcriptional signatures. Nuclear YAP1/TAZ expression was assessed by immunohistochemistry (IHC) in 44 patient samples, and genomic structural variations (SVs) were analyzed in 8 SFT specimens through Optical Genome Mapping. Results: NAB2::STAT6 ectopic expression led to Hippo pathway dysregulation and promoted a malignant phenotype, which was partially reversible upon YAP1/TAZ knockdown or dasatinib treatment. Total RNA-seq of SFT local cases confirmed transcriptional inactivation of Hippo signalling and revealed a network linking Hippo and EGR1 pathways. Stronger nuclear YAP1/TAZ staining was observed in relapsed SFT samples compared with primary tumors. The overall genomic stability precluded Hippo pathway deregulation via SVs in clinical samples. Conclusion: NAB2::STAT6 promotes SFT progression by inactivating the Hippo pathway, unveiling a potential targetable vulnerability and further expanding our understanding of NAB2::STAT6-driven oncogenesis. |
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