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Aberrant ERBB4-SRC signaling as a hallmark of group 4 medulloblastoma revealed by integrative phosphoproteomic profiling

The current consensus recognizes four main medulloblastoma subgroups (wingless, Sonic hedgehog, group 3 and group 4). While medulloblastoma subgroups have been characterized extensively at the (epi-)genomic and transcriptomic levels, the proteome and phosphoproteome landscape remain to be comprehens...

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Main Authors: Forget, Antoine (Author) , Brabetz, Sebastian (Author) , Sieber, Laura (Author) , Chavez, Lukas (Author) , Okonechnikov, Konstantin (Author) , Sharma, Tanvi (Author) , Thatikonda, Venu (Author) , Korshunov, Andrey (Author) , Kool, Marcel (Author) , Pfister, Stefan (Author) , Kawauchi, Daisuke (Author)
Format: Article (Journal)
Language:English
Published: September 10, 2018
In: Cancer cell
Year: 2018, Volume: 34, Issue: 3, Pages: 379-395
ISSN:1878-3686
DOI:10.1016/j.ccell.2018.08.002
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ccell.2018.08.002
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S1535610818303568
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Author Notes:Antoine Forget, Loredana Martignetti, Stéphanie Puget, Laurence Calzone, Sebastian Brabetz, Daniel Picard, Arnau Montagud, Stéphane Liva, Alexandre Sta, Florent Dingli, Guillaume Arras, Jaime Rivera, Damarys Loew, Aurore Besnard, Joëlle Lacombe, Mélanie Pagès, Pascale Varlet, Christelle Dufour, Hua Yu, Audrey L. Mercier, Emilie Indersie, Anaïs Chivet, Sophie Leboucher, Laura Sieber, Kevin Beccaria, Michael Gombert, Frauke D. Meyer, Nan Qin, Jasmin Bartl, Lukas Chavez, Konstantin Okonechnikov, Tanvi Sharma, Venu Thatikonda, Franck Bourdeaut, Celio Pouponnot, Vijay Ramaswamy, Andrey Korshunov, Arndt Borkhardt, Guido Reifenberger, Patrick Poullet, Michael D. Taylor, Marcel Kool, Stefan M. Pfister, Daisuke Kawauchi, Emmanuel Barillot, Marc Remke, and Olivier Ayrault
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Summary:The current consensus recognizes four main medulloblastoma subgroups (wingless, Sonic hedgehog, group 3 and group 4). While medulloblastoma subgroups have been characterized extensively at the (epi-)genomic and transcriptomic levels, the proteome and phosphoproteome landscape remain to be comprehensively elucidated. Using quantitative (phospho)-proteomics in primary human medulloblastomas, we unravel distinct posttranscriptional regulation leading to highly divergent oncogenic signaling and kinase activity profiles in groups 3 and 4 medulloblastomas. Specifically, proteomic and phosphoproteomic analyses identify aberrant ERBB4-SRC signaling in group 4. Hence, enforced expression of an activated SRC combined with p53 inactivation induces murine tumors that resemble group 4 medulloblastoma. Therefore, our integrative proteogenomics approach unveils an oncogenic pathway and potential therapeutic vulnerability in the most common medulloblastoma subgroup.
Item Description:Gesehen am 15.04.2020
Physical Description:Online Resource
ISSN:1878-3686
DOI:10.1016/j.ccell.2018.08.002

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