Format:
24
ISSN:
1878-3686
Content:
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.
Note:
Gesehen am 15.04.2020
In:
Cancer cell, Cambridge, Mass. : Cell Press, 2002, 34(2018,3) 379-395, e1-e7, 24 Seiten, 1878-3686
In:
volume:34
In:
year:2018
In:
number:3
In:
pages:379-395
In:
extent:24
Language:
English
DOI:
10.1016/j.ccell.2018.08.002
URL:
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