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The ETS transcription factor ETV5 is a target of activated ALK in neuroblastoma contributing to increased tumour aggressiveness
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- Mus, Liselot M. (author)
- Ghent University
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- Lambertz, Irina (author)
- Ghent University
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- Claeys, Shana (author)
- Ghent University
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- Kumps, Candy (author)
- Ghent University Hospital
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- Van Loocke, Wouter (author)
- Ghent University
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- Van Neste, Christophe (author)
- Ghent University
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- Umapathy, Ganesh (author)
- Gothenburg University,Göteborgs universitet,University of Gothenburg,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Vaapil, Marica (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine
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- Bartenhagen, Christoph (author)
- University of Cologne,University Hospital of Cologne
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- Laureys, Genevieve (author)
- Ghent University,Ghent University Hospital
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- De Wever, Olivier (author)
- Ghent University
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- Bexell, Daniel (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Molekylär barnonkologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Molecular Pediatric Oncology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Fischer, Matthias (author)
- University Hospital of Cologne,University of Cologne
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- Hallberg, Bengt (author)
- University of Gothenburg
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- Schulte, Johannes (author)
- University Hospital Essen,Charité - University Medicine Berlin,German Cancer Research Centre
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- De Wilde, Bram (author)
- Ghent University Hospital,Ghent University
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- Durinck, Kaat (author)
- Ghent University
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- Denecker, Geertrui (author)
- Ghent University
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- De Preter, Katleen (author)
- Ghent University
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- Speleman, Frank (author)
- Ghent University
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(creator_code:org_t)
- 2020-01-14
- 2020
- English.
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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https://www.nature.c...
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Abstract
Subject headings
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- Neuroblastoma is an aggressive childhood cancer arising from sympatho-adrenergic neuronal progenitors. The low survival rates for high-risk disease point to an urgent need for novel targeted therapeutic approaches. Detailed molecular characterization of the neuroblastoma genomic landscape indicates that ALK-activating mutations are present in 10% of primary tumours. Together with other mutations causing RAS/MAPK pathway activation, ALK mutations are also enriched in relapsed cases and ALK activation was shown to accelerate MYCN-driven tumour formation through hitherto unknown ALK-driven target genes. To gain further insight into how ALK contributes to neuroblastoma aggressiveness, we searched for known oncogenes in our previously reported ALK-driven gene signature. We identified ETV5, a bona fide oncogene in prostate cancer, as robustly upregulated in neuroblastoma cells harbouring ALK mutations, and show high ETV5 levels downstream of the RAS/MAPK axis. Increased ETV5 expression significantly impacted migration, invasion and colony formation in vitro, and ETV5 knockdown reduced proliferation in a murine xenograft model. We also established a gene signature associated with ETV5 knockdown that correlates with poor patient survival. Taken together, our data highlight ETV5 as an intrinsic component of oncogenic ALK-driven signalling through the MAPK axis and propose that ETV5 upregulation in neuroblastoma may contribute to tumour aggressiveness.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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To the university's database
- By the author/editor
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Mus, Liselot M.
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Lambertz, Irina
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Claeys, Shana
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Kumps, Candy
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Van Loocke, Wout ...
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Van Neste, Chris ...
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show more...
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Umapathy, Ganesh
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Vaapil, Marica
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Bartenhagen, Chr ...
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Laureys, Genevie ...
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De Wever, Olivie ...
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Bexell, Daniel
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Fischer, Matthia ...
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Hallberg, Bengt
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Schulte, Johanne ...
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De Wilde, Bram
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Durinck, Kaat
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Denecker, Geertr ...
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De Preter, Katle ...
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Speleman, Frank
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Scientific Repor ...
- By the university
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Lund University
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University of Gothenburg