Aberrant ERBB4-SRC Signaling as a Hallmark of Group 4 Medulloblastoma Revealed by Integrative Phosphoproteomic Profiling

被引：105

作者：

Forget, Antoine ^{[1
,2
]}

Martignetti, Loredana ^{[3
,4
,5
,6
]}

Puget, Stephanie ^{[7
]}

Calzone, Laurence ^{[3
,4
,5
,6
]}

Brabetz, Sebastian ^{[8
,9
,10
]}

Picard, Daniel ^{[11
,12
,13
,29
]}

Montagud, Arnau ^{[3
,4
,5
,6
]}

Liva, Stephane ^{[3
,4
,5
,6
]}

Sta, Alexandre ^{[3
,4
,5
,6
]}

Dingli, Florent ^{[14
]}

Arras, Guillaume ^{[14
]}

Rivera, Jaime ^{[14
]}

Loew, Damarys ^{[14
]}

Besnard, Aurore ^{[15
,31
]}

Lacombe, Joelle ^{[15
,31
]}

Pages, Melanie ^{[15
,31
]}

Varlet, Pascale ^{[15
,31
]}

Dufour, Christelle ^{[16
]}

Yu, Hua ^{[1
,2
]}

Mercier, Audrey L. ^{[1
,2
]}

Indersie, Emilie ^{[1
,2
]}

Chivet, Anais ^{[1
,2
]}

Leboucher, Sophie ^{[1
,17
]}

Sieber, Laura ^{[8
,9
,10
]}

Beccaria, Kevin ^{[7
]}

Gombert, Michael ^{[12
]}

Meyer, Frauke D. ^{[11
,12
,13
,29
]}

Qin, Nan ^{[11
,12
,13
,29
]}

Bartl, Jasmin ^{[11
,12
,13
,29
]}

Chavez, Lukas ^{[8
,9
,10
]}

Okonechnikov, Konstantin ^{[8
,9
,10
]}

Sharma, Tanvi ^{[8
,9
,10
]}

Thatikonda, Venu ^{[8
,9
,10
]}

Bourdeaut, Franck ^{[18
,30
]}

Pouponnot, Celio ^{[1
,2
]}

Ramaswamy, Vijay ^{[19
,20
]}

Korshunov, Andrey ^{[21
]}

Borkhardt, Arndt ^{[12
]}

Reifenberger, Guido ^{[13
]}

Poullet, Patrick ^{[3
,4
,5
,6
]}

Taylor, Michael D. ^{[22
,23
,24
,25
,26
,27
]}

Kool, Marcel ^{[8
,9
,10
]}

Pfister, Stefan M. ^{[8
,9
,10
,28
]}

Kawauchi, Daisuke ^{[8
,9
,10
]}

Barillot, Emmanuel ^{[3
,4
,5
,6
]}

Remke, Marc ^{[11
,12
,13
,29
]}

Ayrault, Olivier ^{[1
,2
]}

机构：

[1] PSL Res Univ, CNRS, INSERM, Inst Curie,UMR, Orsay, France

[2] Univ Paris Saclay, Univ Paris Sud, CNRS, INSERM,U1021,UMR 3347, Orsay, France

[3] Inst Curie, 26 Rue Ulm, F-75005 Paris, France

[4] PSL Res Univ, F-75005 Paris, France

[5] INSERM, U900, F-75005 Paris, France

[6] Mines Paris Tech, F-77305 Fontainebleau, France

[7] Univ Paris 05, Necker Univ Hosp, Sorbonne Paris Cite, Dept Pediat Neurosurg, F-75015 Paris, France

[8] NCT Heidelberg KiTZ, Hopp Childrens Canc, Heidelberg, Germany

[9] German Canc Res Ctr, Div Pediat Neurooncol, Heidelberg, Germany

[10] German Canc Consortium DKTK, Heidelberg, Germany

[11] DKFZ, Dept Pediat Neurooncogen, Heidelberg, Germany

[12] Univ Hosp Dusseldorf, Med Fac, Dept Pediat Oncol Hematol & Clin Immunol, Dusseldorf, Germany

[13] Heinrich Heine Univ Dusseldorf, Med Fac, Inst Neuropathol, Dusseldorf, Germany

[14] PSL Res Univ, Inst Curie, Prote & Mass Spectrometry Lab, F-75005 Paris, France

[15] St Anna Hosp, Dept Neuropathol, F-75014 Paris, France

[16] Gustave Roussy, Dept Pediat & Adolescent Oncol, Rue Edouard Vaillant, F-94805 Villejuif, France

[17] Ctr Rech, Inst Curie, Plateforme Histol, F-91405 Orsay, France

[18] Paris Sci Lettres Res Univ, Inst Curie, Res Ctr, SiRIC,Lab Translat Res Pediat Oncol, F-75005 Paris, France

[19] Hosp Sick Children, Div Haematol Oncol, Toronto, ON, Canada

[20] Hosp Sick Children, Dept Paediat, Toronto, ON, Canada

[21] Heidelberg Univ Hosp, German Canc Res Ctr DKFZ, Clin Cooperat Unit Neuropathol G380, Heidelberg, Germany

[22] Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON, Canada

[23] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada

[24] Hosp Sick Children, Div Neurosurg, Toronto, ON, Canada

[25] Univ Toronto, Dept Surg, Toronto, ON, Canada

[26] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[27] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

[28] Univ Heidelberg Hosp, Dept Pediat Hematol & Oncol, Heidelberg, Germany

[29] DKTK, Partner Site, Essen, Germany

[30] Paris Sci Lettres Res Univ, INSERM, U830, Inst Curie Res Ctr,Lab Biol & Genet Canc, F-75005 Paris, France

[31] Univ Paris 05, Sorbonne Paris Cite, F-75015 Paris, France

来源：

CANCER CELL | 2018年 / 34卷 / 03期

关键词：

MYC-DRIVEN MEDULLOBLASTOMA; CHILDHOOD MEDULLOBLASTOMA; OUTCOME PREDICTION; PROTEOGENOMIC CHARACTERIZATION; QUANTITATIVE PROTEOMICS; MOLECULAR SUBGROUPS; SHH MEDULLOBLASTOMA; CURRENT CONSENSUS; HUMAN COLON; CANCER;

D O I：

10.1016/j.ccell.2018.08.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：379 / +

页数：24

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