dc.contributor.author	Alshangiti, Amnah M.	en
dc.contributor.author	Wyatt, Sean L.	en
dc.contributor.author	McCarthy, Erin	en
dc.contributor.author	Collins, Louise M.	en
dc.contributor.author	Hegarty, Shane V.	en
dc.contributor.author	Sullivan, Aideen M.	en
dc.contributor.author	O'Keeffe, Gerard W.	en
dc.contributor.funder	Government of Saudi Arabia	en
dc.contributor.funder	Irish Research Council	en
dc.contributor.funder	Science Foundation Ireland	en
dc.date.accessioned	2024-05-23T13:31:31Z
dc.date.available	2024-05-23T13:31:31Z
dc.date.issued	2020	en
dc.description.abstract	Neuroblastoma (NB) is a paediatric cancer that arises in the sympathetic nervous system. Patients with stage 4 tumours have poor outcomes and 20% of high-risk cases have MYCN amplification. The bone morphogenetic proteins (BMPs) play roles in sympathetic neuritogenesis, by signalling through bone morphogenetic protein receptor (BMPR)2 and either BMPR1A or BMPR1B. Alterations in BMPR2 expression have been reported in NB; it is unknown if the expression of BMPR1A or BMPR1B is altered. We report lower BMPR2 and BMPR1B, and higher BMPR1A, expression in stage 4 and in MYCN-amplified NB. Kaplan–Meier plots showed that high BMPR2 or BMPR1B expression was linked to better survival, while high BMPR1A was linked to worse survival. Gene ontology enrichment and pathway analyses revealed that BMPR2 and BMPR1B co-expressed genes were enriched in those associated with NB differentiation. BMPR1A co-expressed genes were enriched in those associated with cell proliferation. Moreover, the correlation between BMPR2 and BMPR1A was strengthened, while the correlation between BMPR2 and BMPR1B was lost, in MYCN-amplified NB. This suggested that differentiation should decrease BMPR1A and increase BMPR1B expression. In agreement, nerve growth factor treatment of cultured sympathetic neurons decreased Bmpr1a expression and increased Bmpr1b expression. Overexpression of dominant negative BMPR1B, treatment with a BMPR1B inhibitor and treatment with GDF5, which signals via BMPR1B, showed that BMPR1B signalling is required for optimal neuritogenesis in NB cells, suggesting that loss of BMPR1B may alter neuritogenesis. The present study shows that expression of distinct BMPRs is associated with different survival outcomes in NB.	en
dc.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.articleid	NS20200006	en
dc.identifier.citation	Alshangiti, A.M., Wyatt, S.L., McCarthy, E., Collins, L.M., Hegarty, S.V., Sullivan, A.M. and O’Keeffe, G.W. (2020) ‘Association of distinct type 1 bone morphogenetic protein receptors with different molecular pathways and survival outcomes in neuroblastoma’, Neuronal Signaling, 4(1), NS20200006 (11pp). doi: 10.1042/NS20200006	en
dc.identifier.doi	10.1042/NS20200006	en
dc.identifier.eissn	2059-6553
dc.identifier.endpage	11	en
dc.identifier.issued	1	en
dc.identifier.journaltitle	Neuronal Signaling	en
dc.identifier.startpage	1	en
dc.identifier.uri	https://hdl.handle.net/10468/15903
dc.identifier.volume	4	en
dc.language.iso	en	en
dc.publisher	Portland Press	en
dc.relation.project	info:eu-repo/grantAgreement/SFI/SFI Career Development Award/15/CDA/3498/IE/Development of GDF5 neurotrophic factor therapy for Parkinson’s disease./	en
dc.rights	© 2020 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).	en
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	en
dc.subject	BMPR	en
dc.subject	Bone morphogenetic protein	en
dc.subject	Neurite growth	en
dc.subject	Neuroblastoma	en
dc.subject	Smad	en
dc.subject	Survival	en
dc.title	Association of distinct type 1 bone morphogenetic protein receptors with different molecular pathways and survival outcomes in neuroblastoma	en
dc.type	Article (peer-reviewed)	en

Association of distinct type 1 bone morphogenetic protein receptors with different molecular pathways and survival outcomes in neuroblastoma

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