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The ETV5 oncogene is a target of activated ALK signaling in neuroblastoma

Liselot Mus UGent, Irina Lambertz, Candy Kumps, Shana Claeys UGent, Geertrui Denecker UGent, Wouter Van Loocke UGent, Christophe Van Neste UGent, Jan Koster, Rogier Versteeg, Nadine Van Roy UGent, et al. (2017) OncoPoint, 5th Research seminar, Abstracts.
abstract
Neuroblastoma (NB) is an aggressive childhood cancer arising from sympatho-adrenergic neuronal progenitors. Current survival rates are still disappointingly low and novel therapeutic venues are needed to improve them. Mutant ALK is currently the most prominent druggable target being present in 10% of NB patients. Unfortunately, in most instances targeted therapies with single compounds lead to resistance and relapse. Therefore, deeper insights into the ALK downstream pathway is critical to understand resistance mechanisms and to identify additional targets for combination therapy. As part of a broader study aimed at dissecting downstream ALK signaling, we observed robust regulation of the oncogene ETV5 in multiple NB cell lines through the ALK-activated RAS/MAPK-axis. Further functional analysis revealed that ALK-mutated NB cell lines depend on ETV5 for proliferation, invasion and colony formation. The effect of ETV5 on proliferation was further supported by mouse xenografts for a NB cell line with stable ETV5 knock-down. Next, transcriptome profiling of both ETV5 knock-down cell lines and xenografts revealed an ETV5 signature which (1) identified patients with poor overall survival, (2) was enriched for an Ewing sarcoma gene signature, suggesting a possible common perturbed gene regulatory pathway and (3) contained CXCR4, an important mediator of invasion and metastasis, and TRIM67, a negative regulator of the RAS-pathway, as possible ETV5 targets. Taken together, we identified ETV5 as an important ALK-MAPK target gene impacting on the ALK driven oncogenic phenotype with CXCR4 and TRIM67 as putative ETV5 effectors which may explain aggressive behaviour and therapy resistance of NB cells.
Please use this url to cite or link to this publication:
author
organization
year
type
conference (meetingAbstract)
publication status
published
subject
in
OncoPoint, 5th Research seminar, Abstracts
conference name
5th OncoPoint research seminar
conference location
Ghent, Belgium
conference start
2017-03-15
conference end
2017-03-15
language
English
UGent publication?
yes
classification
C3
id
8516924
handle
http://hdl.handle.net/1854/LU-8516924
date created
2017-04-04 16:01:56
date last changed
2017-04-10 13:46:57
@inproceedings{8516924,
  abstract     = {Neuroblastoma (NB) is an aggressive childhood cancer arising from sympatho-adrenergic neuronal progenitors. Current survival rates are still disappointingly low and novel therapeutic venues are needed to improve them. Mutant ALK is currently the most prominent druggable target being present in 10\% of NB patients.  Unfortunately, in most instances targeted therapies with single compounds lead to resistance and relapse. Therefore, deeper insights into the ALK downstream pathway is critical to understand resistance mechanisms and to identify additional targets for combination therapy. 
As part of a broader study aimed at dissecting downstream ALK signaling, we observed robust regulation of the oncogene ETV5 in multiple NB cell lines through the ALK-activated RAS/MAPK-axis. Further functional analysis revealed that ALK-mutated NB cell lines depend on ETV5 for proliferation, invasion and colony formation. The effect of ETV5 on proliferation was further supported by mouse xenografts for a NB cell line with stable ETV5 knock-down. Next, transcriptome profiling of both ETV5 knock-down cell lines and xenografts revealed an ETV5 signature which (1) identified patients with poor overall survival, (2) was enriched for an Ewing sarcoma gene signature, suggesting a possible common perturbed gene regulatory pathway and (3) contained CXCR4, an important mediator of invasion and metastasis, and TRIM67, a negative regulator of the RAS-pathway, as possible ETV5 targets. 
Taken together, we identified ETV5 as an important ALK-MAPK target gene impacting on the ALK driven oncogenic phenotype with CXCR4 and TRIM67 as putative ETV5 effectors which may explain aggressive behaviour and therapy resistance of NB cells.},
  author       = {Mus, Liselot and Lambertz, Irina and Kumps, Candy and Claeys, Shana and Denecker, Geertrui and Van Loocke, Wouter and Van Neste, Christophe and Koster, Jan and Versteeg, Rogier and Van Roy, Nadine and De Wilde, Bram and Laureys, Genevieve and Schulte, Johannes and De Wever, Olivier and De Preter, Katleen and Speleman, Franki},
  booktitle    = {OncoPoint, 5th Research seminar, Abstracts},
  language     = {eng},
  location     = {Ghent, Belgium},
  title        = {The ETV5 oncogene is a target of activated ALK signaling in neuroblastoma},
  year         = {2017},
}

Chicago
Mus, Liselot, Irina Lambertz, Candy Kumps, Shana Claeys, Geertrui Denecker, Wouter Van Loocke, Christophe Van Neste, et al. 2017. “The ETV5 Oncogene Is a Target of Activated ALK Signaling in Neuroblastoma.” In OncoPoint, 5th Research Seminar, Abstracts.
APA
Mus, L., Lambertz, I., Kumps, C., Claeys, S., Denecker, G., Van Loocke, W., Van Neste, C., et al. (2017). The ETV5 oncogene is a target of activated ALK signaling in neuroblastoma. OncoPoint, 5th Research seminar, Abstracts. Presented at the 5th OncoPoint research seminar.
Vancouver
1.
Mus L, Lambertz I, Kumps C, Claeys S, Denecker G, Van Loocke W, et al. The ETV5 oncogene is a target of activated ALK signaling in neuroblastoma. OncoPoint, 5th Research seminar, Abstracts. 2017.
MLA
Mus, Liselot, Irina Lambertz, Candy Kumps, et al. “The ETV5 Oncogene Is a Target of Activated ALK Signaling in Neuroblastoma.” OncoPoint, 5th Research Seminar, Abstracts. 2017. Print.