Cargando…
CREB signaling activity correlates with differentiation and survival in medulloblastoma
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 rep...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352923/ https://www.ncbi.nlm.nih.gov/pubmed/34373489 http://dx.doi.org/10.1038/s41598-021-95381-0 |
_version_ | 1783736292768481280 |
---|---|
author | Armandari, Inna Zomerman, Walderik W. Plasschaert, Sabine L. A. Smit, Marlinde J. Martini, Tosca. E. I. de Camargo Magalhães, Eduardo S. Hogeling, Shanna M. Rozema-Huizinga, Geesina C. Lourens, Harm J. Meeuwsen-de Boer, Tiny G. J. Scherpen, Frank J. G. de Bont, Eveline S. J. M. Bruggeman, Sophia W. M. |
author_facet | Armandari, Inna Zomerman, Walderik W. Plasschaert, Sabine L. A. Smit, Marlinde J. Martini, Tosca. E. I. de Camargo Magalhães, Eduardo S. Hogeling, Shanna M. Rozema-Huizinga, Geesina C. Lourens, Harm J. Meeuwsen-de Boer, Tiny G. J. Scherpen, Frank J. G. de Bont, Eveline S. J. M. Bruggeman, Sophia W. M. |
author_sort | Armandari, Inna |
collection | PubMed |
description | 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 | Online Article Text |
id | pubmed-8352923 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-83529232021-08-11 CREB signaling activity correlates with differentiation and survival in medulloblastoma Armandari, Inna Zomerman, Walderik W. Plasschaert, Sabine L. A. Smit, Marlinde J. Martini, Tosca. E. I. de Camargo Magalhães, Eduardo S. Hogeling, Shanna M. Rozema-Huizinga, Geesina C. Lourens, Harm J. Meeuwsen-de Boer, Tiny G. J. Scherpen, Frank J. G. de Bont, Eveline S. J. M. Bruggeman, Sophia W. M. Sci Rep Article 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. Nature Publishing Group UK 2021-08-09 /pmc/articles/PMC8352923/ /pubmed/34373489 http://dx.doi.org/10.1038/s41598-021-95381-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Armandari, Inna Zomerman, Walderik W. Plasschaert, Sabine L. A. Smit, Marlinde J. Martini, Tosca. E. I. de Camargo Magalhães, Eduardo S. Hogeling, Shanna M. Rozema-Huizinga, Geesina C. Lourens, Harm J. Meeuwsen-de Boer, Tiny G. J. Scherpen, Frank J. G. de Bont, Eveline S. J. M. Bruggeman, Sophia W. M. CREB signaling activity correlates with differentiation and survival in medulloblastoma |
title | 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_short | CREB signaling activity correlates with differentiation and survival in medulloblastoma |
title_sort | creb signaling activity correlates with differentiation and survival in medulloblastoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352923/ https://www.ncbi.nlm.nih.gov/pubmed/34373489 http://dx.doi.org/10.1038/s41598-021-95381-0 |
work_keys_str_mv | AT armandariinna crebsignalingactivitycorrelateswithdifferentiationandsurvivalinmedulloblastoma AT zomermanwalderikw crebsignalingactivitycorrelateswithdifferentiationandsurvivalinmedulloblastoma AT plasschaertsabinela crebsignalingactivitycorrelateswithdifferentiationandsurvivalinmedulloblastoma AT smitmarlindej crebsignalingactivitycorrelateswithdifferentiationandsurvivalinmedulloblastoma AT martinitoscaei crebsignalingactivitycorrelateswithdifferentiationandsurvivalinmedulloblastoma AT decamargomagalhaeseduardos crebsignalingactivitycorrelateswithdifferentiationandsurvivalinmedulloblastoma AT hogelingshannam crebsignalingactivitycorrelateswithdifferentiationandsurvivalinmedulloblastoma AT rozemahuizingageesinac crebsignalingactivitycorrelateswithdifferentiationandsurvivalinmedulloblastoma AT lourensharmj crebsignalingactivitycorrelateswithdifferentiationandsurvivalinmedulloblastoma AT meeuwsendeboertinygj crebsignalingactivitycorrelateswithdifferentiationandsurvivalinmedulloblastoma AT scherpenfrankjg crebsignalingactivitycorrelateswithdifferentiationandsurvivalinmedulloblastoma AT debontevelinesjm crebsignalingactivitycorrelateswithdifferentiationandsurvivalinmedulloblastoma AT bruggemansophiawm crebsignalingactivitycorrelateswithdifferentiationandsurvivalinmedulloblastoma |