CREB signaling activity correlates with differentiation and survival in medulloblastoma.

Autor: Armandari I; Department of Ageing Biology/ERIBA, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, the Netherlands.; Department of Histology and Cell Biology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Sekip Utara, 55281, Yogyakarta, Indonesia., Zomerman WW; Department of Pediatric Oncology and Hematology/Pediatrics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands., Plasschaert SLA; Princess Máxima Center for Pediatric Oncology, Lundlaan 6, 3584 EA, Utrecht, The Netherlands., Smit MJ; Department of Ageing Biology/ERIBA, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, the Netherlands., Martini TEI; Department of Ageing Biology/ERIBA, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, the Netherlands., de Camargo Magalhães ES; Department of Ageing Biology/ERIBA, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, the Netherlands.; Glial Cell Biology Laboratory, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, 21949-590, Brazil., Hogeling SM; Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands., Rozema-Huizinga GC; Department of Ageing Biology/ERIBA, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, the Netherlands., Lourens HJ; Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands., Meeuwsen-de Boer TGJ; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands., Scherpen FJG; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands., de Bont ESJM; Department of Pediatric Oncology and Hematology/Pediatrics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands., Bruggeman SWM; Department of Ageing Biology/ERIBA, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, the Netherlands. s.w.m.bruggeman@umcg.nl.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Aug 09; Vol. 11 (1), pp. 16077. Date of Electronic Publication: 2021 Aug 09.
DOI: 10.1038/s41598-021-95381-0
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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