CREB signaling activity correlates with differentiation and survival in medulloblastoma

Abstract While there has been significant progress in the molecular characterization of the childhood brain cancer medulloblastoma, the tumor proteome remains less explored. However, it is important to obtain a complete understanding of medulloblastoma protein biology, since interactions between pro...

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Autores principales:	Inna Armandari, Walderik W. Zomerman, Sabine L. A. Plasschaert, Marlinde J. Smit, Tosca. E. I. Martini, Eduardo S. de Camargo Magalhães, Shanna M. Hogeling, Geesina C. Rozema-Huizinga, Harm J. Lourens, Tiny G. J. Meeuwsen-de Boer, Frank J. G. Scherpen, Eveline S. J. M. de Bont, Sophia W. M. Bruggeman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4b52aa87cc92410bae837f1ba12b32f3
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spelling	oai:doaj.org-article:4b52aa87cc92410bae837f1ba12b32f32021-12-02T19:06:33ZCREB signaling activity correlates with differentiation and survival in medulloblastoma10.1038/s41598-021-95381-02045-2322https://doaj.org/article/4b52aa87cc92410bae837f1ba12b32f32021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95381-0https://doaj.org/toc/2045-2322Abstract While there has been significant progress in the molecular characterization of the childhood brain cancer medulloblastoma, the tumor proteome remains less explored. However, it is important to obtain a complete understanding of medulloblastoma protein biology, since interactions between proteins represent potential new drug targets. Using previously generated phosphoprotein signaling-profiles of a large cohort of primary medulloblastoma, we discovered that phosphorylation of transcription factor CREB strongly correlates with medulloblastoma survival and associates with a differentiation phenotype. We further found that during normal cerebellar development, phosphorylated CREB was selectively expressed in differentiating cerebellar granule neuron progenitor (CGNP) cells. In line, we observed increased differentiation in CGNPs treated with Forskolin, Bmp6 and Bmp12 (Gdf7), which induce CREB phosphorylation. Lastly, we demonstrated that inducing CREB activation via PKA-mediated CREB signaling, but not Bmp/MEK/ERK mediated signalling, enhances medulloblastoma cell sensitivity to chemotherapy.Inna ArmandariWalderik W. ZomermanSabine L. A. PlasschaertMarlinde J. SmitTosca. E. I. MartiniEduardo S. de Camargo MagalhãesShanna M. HogelingGeesina C. Rozema-HuizingaHarm J. LourensTiny G. J. Meeuwsen-de BoerFrank J. G. ScherpenEveline S. J. M. de BontSophia W. M. BruggemanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Inna Armandari Walderik W. Zomerman Sabine L. A. Plasschaert Marlinde J. Smit Tosca. E. I. Martini Eduardo S. de Camargo Magalhães Shanna M. Hogeling Geesina C. Rozema-Huizinga Harm J. Lourens Tiny G. J. Meeuwsen-de Boer Frank J. G. Scherpen Eveline S. J. M. de Bont Sophia W. M. Bruggeman CREB signaling activity correlates with differentiation and survival in medulloblastoma
description	Abstract While there has been significant progress in the molecular characterization of the childhood brain cancer medulloblastoma, the tumor proteome remains less explored. However, it is important to obtain a complete understanding of medulloblastoma protein biology, since interactions between proteins represent potential new drug targets. Using previously generated phosphoprotein signaling-profiles of a large cohort of primary medulloblastoma, we discovered that phosphorylation of transcription factor CREB strongly correlates with medulloblastoma survival and associates with a differentiation phenotype. We further found that during normal cerebellar development, phosphorylated CREB was selectively expressed in differentiating cerebellar granule neuron progenitor (CGNP) cells. In line, we observed increased differentiation in CGNPs treated with Forskolin, Bmp6 and Bmp12 (Gdf7), which induce CREB phosphorylation. Lastly, we demonstrated that inducing CREB activation via PKA-mediated CREB signaling, but not Bmp/MEK/ERK mediated signalling, enhances medulloblastoma cell sensitivity to chemotherapy.
format	article
author	Inna Armandari Walderik W. Zomerman Sabine L. A. Plasschaert Marlinde J. Smit Tosca. E. I. Martini Eduardo S. de Camargo Magalhães Shanna M. Hogeling Geesina C. Rozema-Huizinga Harm J. Lourens Tiny G. J. Meeuwsen-de Boer Frank J. G. Scherpen Eveline S. J. M. de Bont Sophia W. M. Bruggeman
author_facet	Inna Armandari Walderik W. Zomerman Sabine L. A. Plasschaert Marlinde J. Smit Tosca. E. I. Martini Eduardo S. de Camargo Magalhães Shanna M. Hogeling Geesina C. Rozema-Huizinga Harm J. Lourens Tiny G. J. Meeuwsen-de Boer Frank J. G. Scherpen Eveline S. J. M. de Bont Sophia W. M. Bruggeman
author_sort	Inna Armandari
title	CREB signaling activity correlates with differentiation and survival in medulloblastoma
title_short	CREB signaling activity correlates with differentiation and survival in medulloblastoma
title_full	CREB signaling activity correlates with differentiation and survival in medulloblastoma
title_fullStr	CREB signaling activity correlates with differentiation and survival in medulloblastoma
title_full_unstemmed	CREB signaling activity correlates with differentiation and survival in medulloblastoma
title_sort	creb signaling activity correlates with differentiation and survival in medulloblastoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4b52aa87cc92410bae837f1ba12b32f3
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_version_	1718377147605712896

CREB signaling activity correlates with differentiation and survival in medulloblastoma

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