RT Journal Article
T1 Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis
A1 Chicón-Bosch, Mariona
A1 Costa Fraga, Nicolás
A1 Díaz Lagares, Ángel
A1 Tirado, Òscar M.
K1 CREB1
K1 Ewing sarcoma
K1 FGD4
K1 LOXHD1
K1 Metastasis
K1 Methylomics
K1 Mouse model
K1 Multi-omics
K1 Proteomics
K1 Transcriptomics
AB 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.
PB Wiley
YR 2025
FD 2025-01-05
LK https://hdl.handle.net/10347/44340
UL https://hdl.handle.net/10347/44340
LA eng
NO 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, T. G. P., Díaz-Lagares, Á., Lopez-Alemany, R., & Tirado, Ò. M. (2025). Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis. Molecular Oncology, 19(4), 1002-1028. https://doi.org/10.1002/1878-0261.13788
NO The authors thank Lara Nonell from MARGenomics for her assistance in the initial bioinformatic analyses. This work was supported by grants from Instituto de Salud Carlos III and FEDER (CES12/021). Ministerio de Ciencia, Innovación y Universidades (RTI2018-094787-B-I00; PID2021-122828OB-I00). AGAUR (2017SGR332). La Marató de TV3 (318/C/2019). Alba Pérez Foundation. CERCA Programme/Generalitat de Catalunya. ADL was funded by a contract “Juan Rodés” (JR17/00016) from “Instituto de Salud Carlos III” (ISCIII) and by Servizo Galego de Saúde (SERGAS). NC-F is funded by a predoctoral contract from “Xunta de Galicia” (IN606A-2020/004). The laboratory of TGPG and FCA is supported by the Barbara and Wilfried Mohr foundation, the Dr. Rolf M. Schwiete foundation (2022-031), and is co-funded by the European Union (ERC, CANCER-HARAKIRI, 101122595). Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible for them.
DS Minerva
RD 22 abr 2026