Evidence map›Paper›PMID 27769056›Full record

ArticleOncotarget2016

Nuclear FOXO3 predicts adverse clinical outcome and promotes tumor angiogenesis in neuroblastoma.

Judith Hagenbuchner, Martina Rupp, Christina Salvador, Bernhard Meister, Ursula Kiechl-Kohlendorfer, Thomas Müller, Kathrin Geiger, Consolato Sergi, Petra Obexer, Michael J Ausserlechner

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. DAF-16/FOXO maintains genome integrity following genotoxic stress.bioRxiv : the preprint server for biology · 2025
    Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA.Protein science : a publication of the Protein Society · 2022
    Article
  12. Review
  13. Article
  14. Diverse roles of FOXO family members in gastric cancer.World journal of gastrointestinal oncology · 2021
    Review
  15. The evolving landscape of NMolecular therapy : the journal of the American Society of Gene Therapy · 2021
    Review
  16. Review
  17. The PI3K pathway impacts stem gene expression in a set of glioblastoma cell lines.Journal of cancer research and clinical oncology · 2020
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Judith HagenbuchnerDepartments of Pediatrics II, Medical University Innsbruck, Innsbruck, Austria.
Martina RuppDepartments of Pediatrics II, Medical University Innsbruck, Innsbruck, Austria.
Christina SalvadorPediatrics I, Medical University Innsbruck, Innsbruck, Austria.
Bernhard MeisterPediatrics I, Medical University Innsbruck, Innsbruck, Austria.
Ursula Kiechl-KohlendorferDepartments of Pediatrics II, Medical University Innsbruck, Innsbruck, Austria.
Thomas MüllerPediatrics I, Medical University Innsbruck, Innsbruck, Austria.
Kathrin GeigerTyrolean Cancer Research Institute, Innsbruck, Austria.
Consolato SergiWalter C. Mackenzie Centre, University of Alberta, Edmonton, Canada.
Petra ObexerDepartments of Pediatrics II, Medical University Innsbruck, Innsbruck, Austria.
Michael J AusserlechnerPediatrics I, Medical University Innsbruck, Innsbruck, Austria.
Innsbruck Medical University · ATTyrolean Cancer Research Institute · ATUniversity of Alberta · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neuroblastoma is the most frequent, extracranial solid tumor in children with still poor prognosis in stage IV disease. In this study, we analyzed FOXO3-phosphorylation and cellular localization in tumor biopsies and determined the function of this homeostasis regulator in vitro and in vivo. FOXO3-phosphorylation at threonine-32 (T32) and nuclear localization in biopsies significantly correlated with stage IV disease. DNA-damaging drugs induced nuclear accumulation of FOXO3, which was associated with elevated T32-phosphorylation in stage IV-derived neuroblastoma cells, thereby reflecting the in situ results. In contrast, hypoxic conditions repressed PKB-activity and caused dephosphorylation of FOXO3 in both, stroma-like SH-EP and high-stage-derived STA-NB15 cells. The activation of an ectopically-expressed FOXO3 in these cells reduced viability at normoxia, but promoted growth at hypoxic conditions and elevated VEGF-C-expression. In chorioallantoic membrane (CAM) assays STA-NB15 tumors with ectopic FOXO3 showed increased micro-vessel formation and, when xenografted into nude mice, a gene-dosage-dependent effect of FOXO3 in high-stage STA-NB15 cells became evident: low-level activation increased tumor-vascularization, whereas hyper-activation repressed tumor growth.The combined data suggest that, depending on the mode and intensity of activation, cellular FOXO3 acts as a homeostasis regulator promoting tumor growth at hypoxic conditions and tumor angiogenesis in high-stage neuroblastoma.

Indexed as

AnimalsCell HypoxiaCell Line, TumorCell NucleusCell ProliferationCell SurvivalFemaleForkhead Box Protein O3Gene DosageHumansMiceNeoplasm StagingNeoplasm TransplantationNeuroblastomaPhosphorylationPrognosisForkhead Box Protein O3FOXO3 protein, humanThreoninechemotherapychorioallantoic membrane (CAM)hypoxia

Identifiers

PMID27769056
PMCPMC5363607
OpenAlexW2534856436

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.