Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.
Por:
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 and Tirado, OM
Publicada:
1 abr 2025
Ahead of Print:
5 ene 2025
Resumen:
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.
Filiaciones:
Chicón-Bosch, M:
Inst Invest Biomed Bellvitge IDIBELL, Sarcoma Res Grp, Oncobell, Barcelona, Spain
Hosp Duran & Reynals, Inst Invest Biomed Bellvitge IDIBELL, Oncobell, Gran Via 199,3a Planta, Barcelona 08908, Spain
Sánchez-Serra, S:
Inst Invest Biomed Bellvitge IDIBELL, Sarcoma Res Grp, Oncobell, Barcelona, Spain
Univ Barcelona UB, Barcelona, Spain
Rosàs-Lapeña, M:
Inst Invest Biomed Bellvitge IDIBELL, Sarcoma Res Grp, Oncobell, Barcelona, Spain
Costa-Fraga, N:
Univ Clin Hosp Santiago CHUS SERGAS, Epigen Unit, Canc Epigen, Translat Med Oncol Grp ONCOMET,Hlth Res Inst Santi, Santiago De Compostela, Spain
Univ Santiago De Compostela USC, Med & Dent Sch, Galician Precis Oncol Res Grp ONCOGAL, Santiago De Compostela, Spain
Univ Santiago de Compostela USC, Santiago De Compostela, Spain
Univ Hosp Complex Santiago de Compostela CHUS, Dept Clin Anal, Santiago De Compostela, Spain
Besalú-Velázquez, J:
Inst Invest Biomed Bellvitge IDIBELL, Sarcoma Res Grp, Oncobell, Barcelona, Spain
Illa-Bernadí, J:
Inst Invest Biomed Bellvitge IDIBELL, Sarcoma Res Grp, Oncobell, Barcelona, Spain
Mateo-Lozano S:
Hosp St Joan de Deu, Inst Recerca St Joan de Deu, Dev Tumor Biol Lab, Barcelona, Spain
Hosp St Joan de Deu, Pediat Canc Ctr Barcelona, Barcelona, Spain
Cidre-Aranaz, F:
German Canc Res Ctr, German Canc Consortium DKTK, Div Translat Paediat Sarcoma Res, Heidelberg, Germany
Hopp Childrens Canc Ctr KiTZ, Heidelberg, Germany
NCT Heidelberg, Natl Ctr Tumor Dis NCT, Heidelberg, Germany
Grünewald, TGP:
German Canc Res Ctr, German Canc Consortium DKTK, Div Translat Paediat Sarcoma Res, Heidelberg, Germany
Hopp Childrens Canc Ctr KiTZ, Heidelberg, Germany
NCT Heidelberg, Natl Ctr Tumor Dis NCT, Heidelberg, Germany
Heidelberg Univ Hosp, Inst Pathol, Heidelberg, Germany
Díaz-Lagares, A:
Univ Clin Hosp Santiago CHUS SERGAS, Epigen Unit, Canc Epigen, Translat Med Oncol Grp ONCOMET,Hlth Res Inst Santi, Santiago De Compostela, Spain
Univ Santiago De Compostela USC, Med & Dent Sch, Galician Precis Oncol Res Grp ONCOGAL, Santiago De Compostela, Spain
Univ Santiago de Compostela USC, Santiago De Compostela, Spain
Univ Hosp Complex Santiago de Compostela CHUS, Dept Clin Anal, Santiago De Compostela, Spain
Carlos III Inst Hlth ISCIII, CIBERONC, Madrid, Spain
Lopez-Alemany, R:
Inst Invest Biomed Bellvitge IDIBELL, Sarcoma Res Grp, Oncobell, Barcelona, Spain
Tirado, OM:
Carlos III Inst Hlth ISCIII, CIBERONC, Madrid, Spain
Inst Catala Oncol ICO, Barcelona, Spain
Hosp Duran & Reynals, Inst Invest Biomed Bellvitge IDIBELL, Oncobell, Gran Via 199,3a Planta, Barcelona 08908, Spain
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