| Literature DB >> 30205043 |
Antoine Forget1, Loredana Martignetti2, Stéphanie Puget3, Laurence Calzone2, Sebastian Brabetz4, Daniel Picard5, Arnau Montagud2, Stéphane Liva2, Alexandre Sta2, Florent Dingli6, Guillaume Arras6, Jaime Rivera6, Damarys Loew6, Aurore Besnard7, Joëlle Lacombe7, Mélanie Pagès7, Pascale Varlet7, Christelle Dufour8, Hua Yu9, Audrey L Mercier9, Emilie Indersie9, Anaïs Chivet9, Sophie Leboucher10, Laura Sieber4, Kevin Beccaria3, Michael Gombert11, Frauke D Meyer5, Nan Qin5, Jasmin Bartl5, Lukas Chavez4, Konstantin Okonechnikov4, Tanvi Sharma4, Venu Thatikonda4, Franck Bourdeaut12, Celio Pouponnot9, Vijay Ramaswamy13, Andrey Korshunov14, Arndt Borkhardt11, Guido Reifenberger15, Patrick Poullet2, Michael D Taylor16, Marcel Kool4, Stefan M Pfister17, Daisuke Kawauchi18, Emmanuel Barillot19, Marc Remke20, Olivier Ayrault21.
Abstract
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.Entities:
Keywords: medulloblastoma; multi-omics; proteomics
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Year: 2018 PMID： 30205043 DOI： 10.1016/j.ccell.2018.08.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743