EIF4EBP1 is transcriptionally upregulated by MYCN and associates with poor prognosis in neuroblastoma
Neuroblastoma (NB) accounts for 15% of cancer-related deaths in childhood despite considerable therapeutic improvements. While several risk factors, including MYCN amplification and alterations in RAS and p53 pathway genes, have been defined in NB, the clinical outcome is very variable and difficult...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
04 April 2022
|
| In: |
Cell death discovery
Year: 2022, Volume: 8, Pages: 1-12 |
| ISSN: | 2058-7716 |
| DOI: | 10.1038/s41420-022-00963-0 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41420-022-00963-0 Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41420-022-00963-0 
|
| Author Notes: | Kai Voeltzke, Katerina Scharov, Cornelius Maximilian Funk, Alisa Kahler, Daniel Picard, Laura Hauffe, Martin F. Orth, Marc Remke, Irene Esposito, Thomas Kirchner, Alexander Schramm, Barak Rotblat, Thomas G.P. Grünewald, Guido Reifenberger and Gabriel Leprivier |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1817616048 | ||
| 003 | DE-627 | ||
| 005 | 20230118143830.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 220927s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41420-022-00963-0 |2 doi | |
| 035 | |a (DE-627)1817616048 | ||
| 035 | |a (DE-599)KXP1817616048 | ||
| 035 | |a (OCoLC)1361696168 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Völtzke, Kai Philipp |e VerfasserIn |0 (DE-588)1256863955 |0 (DE-627)180101860X |4 aut | |
| 245 | 1 | 0 | |a EIF4EBP1 is transcriptionally upregulated by MYCN and associates with poor prognosis in neuroblastoma |c Kai Voeltzke, Katerina Scharov, Cornelius Maximilian Funk, Alisa Kahler, Daniel Picard, Laura Hauffe, Martin F. Orth, Marc Remke, Irene Esposito, Thomas Kirchner, Alexander Schramm, Barak Rotblat, Thomas G.P. Grünewald, Guido Reifenberger and Gabriel Leprivier |
| 264 | 1 | |c 04 April 2022 | |
| 300 | |a 12 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Published: 04 April 2022 | ||
| 500 | |a Gesehen am 27.09.2022 | ||
| 520 | |a Neuroblastoma (NB) accounts for 15% of cancer-related deaths in childhood despite considerable therapeutic improvements. While several risk factors, including MYCN amplification and alterations in RAS and p53 pathway genes, have been defined in NB, the clinical outcome is very variable and difficult to predict. Since genes of the mechanistic target of rapamycin (mTOR) pathway are upregulated in MYCN-amplified NB, we aimed to define the predictive value of the mTOR substrate-encoding gene eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) expression in NB patients. Using publicly available data sets, we found that EIF4EBP1 mRNA expression is positively correlated with MYCN expression and elevated in stage 4 and high-risk NB patients. In addition, high EIF4EBP1 mRNA expression is associated with reduced overall and event-free survival in the entire group of NB patients in three cohorts, as well as in stage 4 and high-risk patients. This was confirmed by monitoring the clinical value of 4EBP1 protein expression, which revealed that high levels of 4EBP1 are significantly associated with prognostically unfavorable NB histology. Finally, functional analyses revealed that EIF4EBP1 expression is transcriptionally controlled by MYCN binding to the EIF4EBP1 promoter in NB cells. Our data highlight that EIF4EBP1 is a direct transcriptional target of MYCN whose high expression is associated with poor prognosis in NB patients. Therefore, EIF4EBP1 may serve to better stratify patients with NB. | ||
| 650 | 4 | |a Paediatric cancer | |
| 650 | 4 | |a Tumour biomarkers | |
| 700 | 1 | |a Scharov, Katerina |e VerfasserIn |0 (DE-588)1257905120 |0 (DE-627)180259003X |4 aut | |
| 700 | 1 | |a Funk, Cornelius M. |d 1996- |e VerfasserIn |0 (DE-588)1269011669 |0 (DE-627)1817668129 |4 aut | |
| 700 | 1 | |a Kahler, Alisa |e VerfasserIn |0 (DE-588)1257909835 |0 (DE-627)1802591060 |4 aut | |
| 700 | 1 | |a Picard, Daniel |e VerfasserIn |0 (DE-588)1170638120 |0 (DE-627)1039832644 |0 (DE-576)512585415 |4 aut | |
| 700 | 1 | |a Hruby, Laura |e VerfasserIn |0 (DE-588)1254082387 |0 (DE-627)1796732559 |4 aut | |
| 700 | 1 | |a Orth, Martin Franz |d 1988- |e VerfasserIn |0 (DE-588)1160610517 |0 (DE-627)1023978040 |0 (DE-576)506047245 |4 aut | |
| 700 | 1 | |a Remke, Marc |d 1981- |e VerfasserIn |0 (DE-588)140368787 |0 (DE-627)618255133 |0 (DE-576)316618179 |4 aut | |
| 700 | 1 | |a Esposito, Irene |d 1972- |e VerfasserIn |0 (DE-588)133482677 |0 (DE-627)638031826 |0 (DE-576)332396282 |4 aut | |
| 700 | 1 | |a Kirchner, Thomas |d 1954- |e VerfasserIn |0 (DE-588)1060659360 |0 (DE-627)800418972 |0 (DE-576)416779174 |4 aut | |
| 700 | 1 | |a Schramm, Alexander |e VerfasserIn |0 (DE-588)120872729X |0 (DE-627)1695294750 |4 aut | |
| 700 | 1 | |a Rotblat, Barak |e VerfasserIn |4 aut | |
| 700 | 1 | |a Grünewald, Thomas G. P. |d 1980- |e VerfasserIn |0 (DE-588)13673426X |0 (DE-627)585870365 |0 (DE-576)301246432 |4 aut | |
| 700 | 1 | |a Reifenberger, Guido |e VerfasserIn |0 (DE-588)1082574740 |0 (DE-627)847675068 |0 (DE-576)455525382 |4 aut | |
| 700 | 1 | |a Leprivier, Gabriel |e VerfasserIn |0 (DE-588)1165184796 |0 (DE-627)1029345058 |0 (DE-576)510295681 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell death discovery |d London : Nature Publishing Group, 2015 |g 8(2022), Artikel-ID 157, Seite 1-12 |h Online-Ressource |w (DE-627)843856351 |w (DE-600)2842546-7 |w (DE-576)453320880 |x 2058-7716 |7 nnas |a EIF4EBP1 is transcriptionally upregulated by MYCN and associates with poor prognosis in neuroblastoma |
| 773 | 1 | 8 | |g volume:8 |g year:2022 |g elocationid:157 |g pages:1-12 |g extent:12 |a EIF4EBP1 is transcriptionally upregulated by MYCN and associates with poor prognosis in neuroblastoma |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41420-022-00963-0 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.nature.com/articles/s41420-022-00963-0 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20220927 | ||
| 993 | |a Article | ||
| 994 | |a 2022 | ||
| 998 | |g 13673426X |a Grünewald, Thomas G. P. |m 13673426X:Grünewald, Thomas G. P. |d 910000 |d 912000 |e 910000PG13673426X |e 912000PG13673426X |k 0/910000/ |k 1/910000/912000/ |p 13 | ||
| 998 | |g 1269011669 |a Funk, Cornelius M. |m 1269011669:Funk, Cornelius M. |d 50000 |e 50000PF1269011669 |k 0/50000/ |p 3 | ||
| 999 | |a KXP-PPN1817616048 |e 4192467291 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"name":{"displayForm":["Kai Voeltzke, Katerina Scharov, Cornelius Maximilian Funk, Alisa Kahler, Daniel Picard, Laura Hauffe, Martin F. Orth, Marc Remke, Irene Esposito, Thomas Kirchner, Alexander Schramm, Barak Rotblat, Thomas G.P. Grünewald, Guido Reifenberger and Gabriel Leprivier"]},"id":{"doi":["10.1038/s41420-022-00963-0"],"eki":["1817616048"]},"recId":"1817616048","physDesc":[{"extent":"12 S."}],"origin":[{"dateIssuedDisp":"04 April 2022","dateIssuedKey":"2022"}],"person":[{"given":"Kai Philipp","role":"aut","family":"Völtzke","display":"Völtzke, Kai Philipp"},{"family":"Scharov","role":"aut","given":"Katerina","display":"Scharov, Katerina"},{"given":"Cornelius M.","role":"aut","family":"Funk","display":"Funk, Cornelius M."},{"display":"Kahler, Alisa","family":"Kahler","role":"aut","given":"Alisa"},{"display":"Picard, Daniel","family":"Picard","role":"aut","given":"Daniel"},{"display":"Hruby, Laura","role":"aut","given":"Laura","family":"Hruby"},{"display":"Orth, Martin Franz","family":"Orth","given":"Martin Franz","role":"aut"},{"display":"Remke, Marc","family":"Remke","role":"aut","given":"Marc"},{"display":"Esposito, Irene","family":"Esposito","role":"aut","given":"Irene"},{"display":"Kirchner, Thomas","given":"Thomas","role":"aut","family":"Kirchner"},{"role":"aut","given":"Alexander","family":"Schramm","display":"Schramm, Alexander"},{"family":"Rotblat","role":"aut","given":"Barak","display":"Rotblat, Barak"},{"family":"Grünewald","given":"Thomas G. P.","role":"aut","display":"Grünewald, Thomas G. P."},{"display":"Reifenberger, Guido","role":"aut","given":"Guido","family":"Reifenberger"},{"family":"Leprivier","given":"Gabriel","role":"aut","display":"Leprivier, Gabriel"}],"relHost":[{"physDesc":[{"extent":"Online-Ressource"}],"recId":"843856351","disp":"EIF4EBP1 is transcriptionally upregulated by MYCN and associates with poor prognosis in neuroblastomaCell death discovery","origin":[{"dateIssuedDisp":"July 2015-","publisherPlace":"London","publisher":"Nature Publishing Group"}],"type":{"media":"Online-Ressource","bibl":"periodical"},"language":["eng"],"note":["Gesehen am 19. September 2016"],"title":[{"title":"Cell death discovery","title_sort":"Cell death discovery"}],"name":{"displayForm":["Cell Death Differentiation Association"]},"pubHistory":["1 (2015)-"],"id":{"zdb":["2842546-7"],"issn":["2058-7716"],"eki":["843856351"]},"part":{"pages":"1-12","year":"2022","text":"8(2022), Artikel-ID 157, Seite 1-12","volume":"8","extent":"12"}}],"title":[{"title":"EIF4EBP1 is transcriptionally upregulated by MYCN and associates with poor prognosis in neuroblastoma","title_sort":"EIF4EBP1 is transcriptionally upregulated by MYCN and associates with poor prognosis in neuroblastoma"}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"language":["eng"],"note":["Published: 04 April 2022","Gesehen am 27.09.2022"]} | ||
| SRT | |a VOELTZKEKAEIF4EBP1IS0420 | ||