Evidence map›Paper›PMID 36115843›Full record

ArticleOncogenesis2022

PFKFB4 interacts with FBXO28 to promote HIF-1α signaling in glioblastoma.

Emma Phillips, Jörg Balss, Frederic Bethke, Stefan Pusch, Stefan Christen, Thomas Hielscher, Martina Schnölzer, Michael N C Fletcher, Antje Habel, Claudia Tessmer and 7 more

Open access · goldAbstract read
In one paragraph

Article in Oncogenesis, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 8% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
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  4. Small-molecule degraders for oncogenic KRASNature communications · 2026
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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

17 authors at 3 institutions in 2 countries.

Emma PhillipsJunior Research Group "Brain Tumor Translational Targets", German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-8946-3284
Jörg BalssJunior Research Group "Brain Tumor Translational Targets", German Cancer Research Center (DKFZ), Heidelberg, Germany.
Frederic BethkeJunior Research Group "Brain Tumor Translational Targets", German Cancer Research Center (DKFZ), Heidelberg, Germany.
Stefan PuschDepartment of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 224, Heidelberg, Germany.
Stefan ChristenLaboratory of Cellular Metabolism and Metabolic Regulation, VIB Center for Cancer Biology, VIB, Herestraat 49, 3000, Leuven, Belgium.
Thomas HielscherDepartment of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
Martina SchnölzerFunctional Proteome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Michael N C FletcherDepartment of Structural and Functional Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Antje HabelDepartment of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 224, Heidelberg, Germany.
Claudia TessmerAntibody Unit, Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Lisa-Marie BrennerJunior Research Group "Brain Tumor Translational Targets", German Cancer Research Center (DKFZ), Heidelberg, Germany.
Mona GöttmannJunior Research Group "Brain Tumor Translational Targets", German Cancer Research Center (DKFZ), Heidelberg, Germany.
David CapperDepartment of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 224, Heidelberg, Germany.
Christel Herold-MendeDivision of Neurosurgical Research, Department of Neurosurgery, University Hospital Heidelberg, INF 400, 69120, Heidelberg, Germany.
Andreas von DeimlingDepartment of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 224, Heidelberg, Germany.
Sarah-Maria FendtLaboratory of Cellular Metabolism and Metabolic Regulation, VIB Center for Cancer Biology, VIB, Herestraat 49, 3000, Leuven, Belgium.
Violaine GoidtsJunior Research Group "Brain Tumor Translational Targets", German Cancer Research Center (DKFZ), Heidelberg, Germany. v.goidts@dkfz.de.ORCID http://orcid.org/0000-0001-9046-4893
German Cancer Research Center · DEHeidelberg University · DEVIB-KU Leuven Center for Cancer Biology · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma is a highly aggressive brain tumor for which there is no cure. The metabolic enzyme 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 4 (PFKFB4) is essential for glioblastoma stem-like cell (GSC) survival but its mode of action is unclear. Understanding the role of PFKFB4 in tumor cell survival could allow it to be leveraged in a cancer therapy. Here, we show the importance of PFKFB4 for glioblastoma growth in vivo in an orthotopic patient derived mouse model. In an evaluation of patient tumor samples of different cancer entities, PFKFB4 protein was found to be overexpressed in prostate, lung, colon, mammary and squamous cell carcinoma, with expression level correlating with tumor grade. Gene expression profiling in PFKFB4-silenced GSCs revealed a downregulation of hypoxia related genes and Western blot analysis confirmed a dramatic reduction of HIF (hypoxia inducible factor) protein levels. Through mass spectrometric analysis of immunoprecipitated PFKFB4, we identified the ubiquitin E3 ligase, F-box only protein 28 (FBXO28), as a new interaction partner of PFKFB4. We show that PFKFB4 regulates the ubiquitylation and subsequent proteasomal degradation of HIF-1α, which is mediated by the ubiquitin ligase activity of FBXO28. This newly discovered function of PFKFB4, coupled with its cancer specificity, provides a new strategy for inhibiting HIF-1α in cancer cells.

Identifiers

PMID36115843
PMCPMC9482633
OpenAlexW4296139755

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.