HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM

Detalles Bibliográficos
Autores: Moura, David S., García-Foncillas López, Jesús Miguel
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/754620
Acceso en línea:https://hdl.handle.net/10486/754620
https://dx.doi.org/10.1007/s00018-024-05250-y
Access Level:acceso abierto
Palabra clave:HMGA1
Soft-tissue sarcoma
Trabectedin
Leiomyosarcoma
mTOR pathway
Medicina
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spelling HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) studyMoura, David S.García-Foncillas López, Jesús MiguelHMGA1Soft-tissue sarcomaTrabectedinLeiomyosarcomamTOR pathwayMedicinaArtículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMHMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively. The effect of HMGA1 silencing on trabectedin activity and gene expression profiling was measured in leiomyosarcoma cells. The effect of combining mTOR inhibitors with trabectedin was assessed on cell viability in vitro studies, whereas in vivo studies tested the activity of this combination. HMGA1 mRNA and protein expression were significantly associated with worse progression-free survival of trabectedin and worse overall survival in STS. HMGA1 silencing sensitized leiomyosarcoma cells for trabectedin treatment, reducing the spheroid area and increasing cell death. The downregulation of HGMA1 significantly decreased the enrichment of some specific gene sets, including the PI3K/AKT/mTOR pathway. The inhibition of mTOR, sensitized leiomyosarcoma cultures for trabectedin treatment, increasing cell death. In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 is an adverse prognostic factor for trabectedin treatment in advanced STS. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growthThis study was partially funded by the Spanish group for research on sarcoma (GEIS; Grant number: GEIS-38) and by PharmaMar (institutional research grant; Grant number: NA)Springer NatureFacultad de MedicinaDepartamento de Medicina20242024-05-17research articlehttp://purl.org/coar/resource_type/c_2df8fbb1EVoRhttp://purl.org/coar/version/c_dc82b40f9837b551info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10486/754620https://dx.doi.org/10.1007/s00018-024-05250-y38758230reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7546202026-06-23T12:46:27Z
dc.title.none.fl_str_mv HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study
title HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study
spellingShingle HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study
Moura, David S.
HMGA1
Soft-tissue sarcoma
Trabectedin
Leiomyosarcoma
mTOR pathway
Medicina
title_short HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study
title_full HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study
title_fullStr HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study
title_full_unstemmed HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study
title_sort HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study
dc.creator.none.fl_str_mv Moura, David S.
García-Foncillas López, Jesús Miguel
author Moura, David S.
author_facet Moura, David S.
García-Foncillas López, Jesús Miguel
author_role author
author2 García-Foncillas López, Jesús Miguel
author2_role author
dc.contributor.none.fl_str_mv Facultad de Medicina
Departamento de Medicina
dc.subject.none.fl_str_mv HMGA1
Soft-tissue sarcoma
Trabectedin
Leiomyosarcoma
mTOR pathway
Medicina
topic HMGA1
Soft-tissue sarcoma
Trabectedin
Leiomyosarcoma
mTOR pathway
Medicina
description Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-05-17
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
EVoR
http://purl.org/coar/version/c_dc82b40f9837b551
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10486/754620
https://dx.doi.org/10.1007/s00018-024-05250-y
38758230
url https://hdl.handle.net/10486/754620
https://dx.doi.org/10.1007/s00018-024-05250-y
identifier_str_mv 38758230
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.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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