Academic Journal
Neural crest-related NXPH1/α-NRXN signaling opposes neuroblastoma malignancy by inhibiting organotropic metastasis
| العنوان: | Neural crest-related NXPH1/α-NRXN signaling opposes neuroblastoma malignancy by inhibiting organotropic metastasis |
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| المؤلفون: | Fanlo, Lucía, Gómez-González, Soledad, Rozalén, Catalina, Pérez-Núñez, Iván, Sangrador, Irene, Tomás-Daza, Laureano, Gautier, Emmanuel L., Usieto, Susana, Rebollo, Elena, Vila-Ubach, Mònica, Carcaboso, Angel M., Javierre, Biola M., Celià-Terrassa, Toni, Lavarino, Cinzia, Martí, Elisa, Dréau, G. le |
| المساهمون: | Ministerio de Ciencia e Innovación (España), Ministerio de Economía y Competitividad (España), Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, European Commission, Agence Nationale de la Recherche (France), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España) |
| بيانات النشر: | Springer Nature |
| سنة النشر: | 2023 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | Metastasis, Paediatric cancer |
| الوصف: | Neuroblastoma is a pediatric cancer that can present as low- or high-risk tumors (LR-NBs and HR-NBs), the latter group showing poor prognosis due to metastasis and strong resistance to current therapy. Whether LR-NBs and HR-NBs differ in the way they exploit the transcriptional program underlying their neural crest, sympatho-adrenal origin remains unclear. Here, we identified the transcriptional signature distinguishing LR-NBs from HR-NBs, which consists mainly of genes that belong to the core sympatho-adrenal developmental program and are associated with favorable patient prognosis and with diminished disease progression. Gain- and loss-of-function experiments revealed that the top candidate gene of this signature, Neurexophilin-1 (NXPH1), has a dual impact on NB cell behavior in vivo: whereas NXPH1 and its receptor α-NRXN1 promote NB tumor growth by stimulating cell proliferation, they conversely inhibit organotropic colonization and metastasis. As suggested by RNA-seq analyses, these effects might result from the ability of NXPH1/α-NRXN signalling to restrain the conversion of NB cells from an adrenergic state to a mesenchymal one. Our findings thus uncover a transcriptional module of the sympatho-adrenal program that opposes neuroblastoma malignancy by impeding metastasis, and pinpoint NXPH1/α-NRXN signaling as a promising target to treat HR-NBs. ; This work was supported by grants from the Ministerio de Ciencia e Innovacion, Gobierno de España (MCINN; BFU2016-81887-REDT and BFU2016-77498-P) and the Asociación Española Contra el Cancer (AECC CI_2016) to EM, from the Fondo de Investigación en Salud (FIS) - Instituto de salud Carlos III (PI14/00038) and the NEN association (Association of Families and Friends of Patients with Neuroblastoma) to CL, from the Instituto de Salud Carlos III-FSE (MS17/00037; PI18/00014; PI21/00020) to TC-T, from Instituto de Salud Carlos III (CP22/00127, co-funded by European Social Fund “Investing in your future”) to BMJ, from the Agence Nationale pour la Recherche ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| تدمد: | 0950-9232 1476-5594 |
| Relation: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/MINECO//BFU2016-81887-REDT; info:eu-repo/grantAgreement/AEI//PRE2019-088005; http://dx.doi.org/10.1038/s41388-023-02742-2; Sí; Oncogene 42: 2218-2233 (2023); http://hdl.handle.net/10261/337299 |
| DOI: | 10.1038/s41388-023-02742-2 |
| الاتاحة: | http://hdl.handle.net/10261/337299 https://doi.org/10.1038/s41388-023-02742-2 |
| Rights: | none |
| رقم الانضمام: | edsbas.24015B9A |
| قاعدة البيانات: | BASE |
| تدمد: | 09509232 14765594 |
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| DOI: | 10.1038/s41388-023-02742-2 |