Detalle de: Aberrant ERBB4-SRC Signaling as a Hallmark of Group 4 Medulloblastoma Revealed by Integrative Phosphoproteomic Profiling
| Title | Aberrant ERBB4-SRC Signaling as a Hallmark of Group 4 Medulloblastoma Revealed by Integrative Phosphoproteomic Profiling |
| 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. |
| Apa Reference | Forget, A., Martignetti, L., Puget, S., Calzone, L., Brabetz, S., Picard, D., Montagud, A., Liva, S., Sta, A., Dingli, F., Arras, G., Rivera, J., Loew, D., Besnard, A., Lacombe, J., Pagès, M., Varlet, P., Dufour, C., Yu, H., … Ayrault, O. (2018). Aberrant ERBB4-SRC Signaling as a Hallmark of Group 4 Medulloblastoma Revealed by Integrative Phosphoproteomic Profiling. Cancer Cell, 34(3), 379-395.e7. 10.1016/j.ccell.2018.08.002 |
| Doi | 10.1016/j.ccell.2018.08.002 |
| Publication Date | Sep 2018 |
| Publication Type | Article |
| Researcher | Arnau Montagud Aquino |
| Ontology | Transcriptomics, Genomics, Proteomics, Phosphoproteomics |
| Research Groups | Systems Biology Modeling |
| Tools |