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...

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Autores: Salguero Aranda, Carmen, Lobo Selma, Laura, Beltrán Povea, Amparo, Baute González, Sergio, Gilabert Prieto, Paula, Jordán Perez, Carmen, Fernández Juárez, José Alberto, Amaral, Ana Teresa, Rodríguez González, René, Díaz Martín, Juan, Álava, Enrique de
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
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spelling Hippo signalling pathway mediates oncogenic properties of NAB2::STAT6 in solitary fibrous tumourSalguero Aranda, CarmenLobo Selma, LauraBeltrán Povea, AmparoBaute González, SergioGilabert Prieto, PaulaJordán Perez, CarmenFernández Juárez, José AlbertoAmaral, Ana TeresaRodríguez González, RenéDíaz Martín, JuanÁlava, Enrique deSolitary fibrous tumourGene fusionNAB2:STAT6Hippo signalling pathwayDasatinibPurpose: 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.Funding for open access publishing: Universidad de Sevilla/ CBUA. This research was funded by Junta de Andalucía (PI-0061- 2020) with assistance to Salguero-Aranda and de Álava; Instituto de Salud Carlos III (PI22/00325) with assistance to Díaz-Martín; Aso-ciación Pablo Ugarte, Fundación María García Estrada, Fundación CRIS contra el cáncer; and FARO Niños con Cáncer. Salguero-Aranda was supported by the Instituto de Salud Carlos III (Sara Borrell post¬doctoral program, 2022), and Díaz-Martín was supported by Servicio Andaluz de Salud (Nicolás Monardes program, Consejería de Salud y Familias, Junta de Andalucía). de Álava’s laboratory is supported by Asociación Española contra el Cáncer (ECAEC222952DEAL), ISCIII-FEDER (PI23-1460), project Ministry of Science of Spain (SARCO¬MATRYX CPP2022-009791), and CIBERONC (CB16/12/00361). R. Rodriguez´s laboratory is supported by CIBERONC (CB16/12/00390). The authors thank the donors and Carolina Castilla from the Hospital Universitario Virgen del Rocío-Instituto de Biomedicina de Sevilla Biobank (Andalusian Public Health System Biobank and ISCIII-Red de Biobancos y Biomodelos-ISCIII-PT20/00069) for the human specimens used in this study, for the assessment and for the technical support provided.Springer NatureUniversidad de Cantabria20262026-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttps://hdl.handle.net/10902/40039Cellular Oncology, 2026, 49(1), 43reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:dnet:ucreareposit::2e4bc25105cd6c9f2be6f562a80721192026-06-02T12:39:31Z
dc.title.none.fl_str_mv Hippo signalling pathway mediates oncogenic properties of NAB2::STAT6 in solitary fibrous tumour
title Hippo signalling pathway mediates oncogenic properties of NAB2::STAT6 in solitary fibrous tumour
spellingShingle Hippo signalling pathway mediates oncogenic properties of NAB2::STAT6 in solitary fibrous tumour
Salguero Aranda, Carmen
Solitary fibrous tumour
Gene fusion
NAB2:STAT6
Hippo signalling pathway
Dasatinib
title_short Hippo signalling pathway mediates oncogenic properties of NAB2::STAT6 in solitary fibrous tumour
title_full Hippo signalling pathway mediates oncogenic properties of NAB2::STAT6 in solitary fibrous tumour
title_fullStr Hippo signalling pathway mediates oncogenic properties of NAB2::STAT6 in solitary fibrous tumour
title_full_unstemmed Hippo signalling pathway mediates oncogenic properties of NAB2::STAT6 in solitary fibrous tumour
title_sort Hippo signalling pathway mediates oncogenic properties of NAB2::STAT6 in solitary fibrous tumour
dc.creator.none.fl_str_mv Salguero Aranda, Carmen
Lobo Selma, Laura
Beltrán Povea, Amparo
Baute González, Sergio
Gilabert Prieto, Paula
Jordán Perez, Carmen
Fernández Juárez, José Alberto
Amaral, Ana Teresa
Rodríguez González, René
Díaz Martín, Juan
Álava, Enrique de
author Salguero Aranda, Carmen
author_facet Salguero Aranda, Carmen
Lobo Selma, Laura
Beltrán Povea, Amparo
Baute González, Sergio
Gilabert Prieto, Paula
Jordán Perez, Carmen
Fernández Juárez, José Alberto
Amaral, Ana Teresa
Rodríguez González, René
Díaz Martín, Juan
Álava, Enrique de
author_role author
author2 Lobo Selma, Laura
Beltrán Povea, Amparo
Baute González, Sergio
Gilabert Prieto, Paula
Jordán Perez, Carmen
Fernández Juárez, José Alberto
Amaral, Ana Teresa
Rodríguez González, René
Díaz Martín, Juan
Álava, Enrique de
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad de Cantabria
dc.subject.none.fl_str_mv Solitary fibrous tumour
Gene fusion
NAB2:STAT6
Hippo signalling pathway
Dasatinib
topic Solitary fibrous tumour
Gene fusion
NAB2:STAT6
Hippo signalling pathway
Dasatinib
description 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.
publishDate 2026
dc.date.none.fl_str_mv 2026
2026-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10902/40039
url https://hdl.handle.net/10902/40039
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv Cellular Oncology, 2026, 49(1), 43
reponame:UCrea Repositorio Abierto de la Universidad de Cantabria
instname:Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
collection UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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