Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.

Ewing sarcoma (EWS) is the second most common bone tumor affecting children and young adults, with dismal outcomes for patients with metastasis at diagnosis. Mechanisms leading to metastasis remain poorly understood. To deepen our knowledge on EWS progression, we have profiled tumors and metastases...

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Autores: Chicón-Bosch, M, Sánchez-Serra, S, Rosàs-Lapeña, M, Costa-Fraga, N, Besalú-Velázquez, J, Illa-Bernadí, J, Mateo-Lozano, S, Cidre-Aranaz, F, Grünewald, TGP, Díaz-Lagares, A, Lopez-Alemany, R, Tirado, OM
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p27382
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=27382
Access Level:acceso abierto
Palabra clave:CREB1
Ewing sarcoma
FGD4
LOXHD1
metastasis
methylomics
mouse model
multi-omics
proteomics
transcriptomics
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spelling Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.Chicón-Bosch, MSánchez-Serra, SRosàs-Lapeña, MCosta-Fraga, NBesalú-Velázquez, JIlla-Bernadí, JMateo-Lozano, SCidre-Aranaz, FGrünewald, TGPDíaz-Lagares, ALopez-Alemany, RTirado, OMCREB1Ewing sarcomaFGD4LOXHD1metastasismethylomicsmouse modelmulti-omicsproteomicstranscriptomicsEwing sarcoma (EWS) is the second most common bone tumor affecting children and young adults, with dismal outcomes for patients with metastasis at diagnosis. Mechanisms leading to metastasis remain poorly understood. To deepen our knowledge on EWS progression, we have profiled tumors and metastases from a spontaneous metastasis mouse model using a multi-omics approach. Combining transcriptomics, proteomics, and methylomics analyses, we identified signaling cascades and candidate genes enriched in metastases that could be modulating aggressiveness in EWS. Phenotypical validation of two of these candidates, cyclic AMP-responsive element-binding protein 1 (CREB1) and lipoxygenase homology domain-containing protein 1 (LOXHD1), showed an association with migration and clonogenic abilities. Moreover, previously described CREB1 downstream targets were present amongst the metastatic-enriched results. Combining the different omics datasets, we identified FYVE, RhoGEF, and PH domain-containing protein 4 (FGD4) as a CREB1 target interconnecting the different EWS biological layers (RNA, protein and methylation status) and whose high expression is associated with worse clinical outcome. Further studies will provide insight into EWS metastasis mechanisms and ultimately improve survival rates for EWS patients.WILEY2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=27382Molecular OncologyISSN: 15747891ISSNe: 18780261reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p273822026-05-27T12:37:41Z
dc.title.none.fl_str_mv Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.
title Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.
spellingShingle Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.
Chicón-Bosch, M
CREB1
Ewing sarcoma
FGD4
LOXHD1
metastasis
methylomics
mouse model
multi-omics
proteomics
transcriptomics
title_short Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.
title_full Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.
title_fullStr Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.
title_full_unstemmed Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.
title_sort Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.
dc.creator.none.fl_str_mv Chicón-Bosch, M
Sánchez-Serra, S
Rosàs-Lapeña, M
Costa-Fraga, N
Besalú-Velázquez, J
Illa-Bernadí, J
Mateo-Lozano, S
Cidre-Aranaz, F
Grünewald, TGP
Díaz-Lagares, A
Lopez-Alemany, R
Tirado, OM
author Chicón-Bosch, M
author_facet Chicón-Bosch, M
Sánchez-Serra, S
Rosàs-Lapeña, M
Costa-Fraga, N
Besalú-Velázquez, J
Illa-Bernadí, J
Mateo-Lozano, S
Cidre-Aranaz, F
Grünewald, TGP
Díaz-Lagares, A
Lopez-Alemany, R
Tirado, OM
author_role author
author2 Sánchez-Serra, S
Rosàs-Lapeña, M
Costa-Fraga, N
Besalú-Velázquez, J
Illa-Bernadí, J
Mateo-Lozano, S
Cidre-Aranaz, F
Grünewald, TGP
Díaz-Lagares, A
Lopez-Alemany, R
Tirado, OM
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CREB1
Ewing sarcoma
FGD4
LOXHD1
metastasis
methylomics
mouse model
multi-omics
proteomics
transcriptomics
topic CREB1
Ewing sarcoma
FGD4
LOXHD1
metastasis
methylomics
mouse model
multi-omics
proteomics
transcriptomics
description Ewing sarcoma (EWS) is the second most common bone tumor affecting children and young adults, with dismal outcomes for patients with metastasis at diagnosis. Mechanisms leading to metastasis remain poorly understood. To deepen our knowledge on EWS progression, we have profiled tumors and metastases from a spontaneous metastasis mouse model using a multi-omics approach. Combining transcriptomics, proteomics, and methylomics analyses, we identified signaling cascades and candidate genes enriched in metastases that could be modulating aggressiveness in EWS. Phenotypical validation of two of these candidates, cyclic AMP-responsive element-binding protein 1 (CREB1) and lipoxygenase homology domain-containing protein 1 (LOXHD1), showed an association with migration and clonogenic abilities. Moreover, previously described CREB1 downstream targets were present amongst the metastatic-enriched results. Combining the different omics datasets, we identified FYVE, RhoGEF, and PH domain-containing protein 4 (FGD4) as a CREB1 target interconnecting the different EWS biological layers (RNA, protein and methylation status) and whose high expression is associated with worse clinical outcome. Further studies will provide insight into EWS metastasis mechanisms and ultimately improve survival rates for EWS patients.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=27382
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=27382
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY
publisher.none.fl_str_mv WILEY
dc.source.none.fl_str_mv Molecular Oncology
ISSN: 15747891
ISSNe: 18780261
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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