Evidence map›Paper›PMID 35474131›Full record

ArticleNeuro-oncology2022

EGFR suppresses p53 function by promoting p53 binding to DNA-PKcs: a noncanonical regulatory axis between EGFR and wild-type p53 in glioblastoma.

Jie Ding, Xiaolong Li, Sabbir Khan, Chen Zhang, Feng Gao, Shayak Sen, Amanda R Wasylishen, Yang Zhao, Guillermina Lozano, Dimpy Koul and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

26 citing papers in PubMed, 41 citations in OpenAlex.

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  12. Current Research Trends in Glioblastoma: Focus on Receptor Tyrosine Kinases.International journal of molecular sciences · 2025
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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

11 authors at 3 institutions in 1 country.

Jie DingDepartment of Neuro-Oncology, Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Xiaolong LiDepartment of Neuro-Oncology, Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Sabbir KhanDepartment of Neuro-Oncology, Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Chen ZhangDepartment of Neuro-Oncology, Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Feng GaoDepartment of Neuro-Oncology, Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Shayak SenDepartment of Neuro-Oncology, Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Amanda R WasylishenDepartment of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Yang ZhaoDepartment of Dermatology, Stanford University School of Medicine, Stanford, California, USA.
Guillermina LozanoDepartment of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Dimpy KoulDepartment of Neuro-Oncology, Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
W K Alfred YungDepartment of Neuro-Oncology, Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
The University of Texas MD Anderson Cancer Center · USStanford University · USThe University of Texas Health Science Center at Houston · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
PATHWAY OF TUMOR SUPPRESSIONR01CA047296 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GUILLERMINA LOZANO · 1993 to 2026
$8.0M
RELATION OF P53 AND OTHER FACTORS IN TRANSGENIC MICER29CA047296 · NCI · UNIVERSITY OF TEXAS MD ANDERSON CAN CTR · PI LOZANO, GUILLERMINA · 1988 to 1992
–
NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA047296
6 · The paper itself

Abstract

backgroundEpidermal growth factor receptor (EGFR) amplification and TP53 mutation are the two most common genetic alterations in glioblastoma multiforme (GBM). A comprehensive analysis of the TCGA GBM database revealed a subgroup with near mutual exclusivity of EGFR amplification and TP53 mutations indicative of a role of EGFR in regulating wild-type-p53 (wt-p53) function. The relationship between EGFR amplification and wt-p53 function remains undefined and this study describes the biological significance of this interaction in GBM.

methodsMass spectrometry was used to identify EGFR-dependent p53-interacting proteins. The p53 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) interaction was detected by co-immunoprecipitation. We used CRISPR-Cas9 gene editing to knockout EGFR and DNA-PKcs and the Edit-R CRIPSR-Cas9 system for conditional knockout of EGFR. ROS activity was measured with a CM-H2DCFDA probe, and real-time PCR was used to quantify expression of p53 target genes.

resultsUsing glioma sphere-forming cells (GSCs), we identified, DNA-PKcs as a p53 interacting protein that functionally inhibits p53 activity. We demonstrate that EGFR knockdown increased wt-p53 transcriptional activity, which was associated with decreased binding between p53 and DNA-PKcs. We further show that inhibition of DNA-PKcs either by siRNA or an inhibitor (nedisertib) increased wt-p53 transcriptional activity, which was not enhanced further by EGFR knockdown, indicating that EGFR suppressed wt-p53 activity through DNA-PKcs binding with p53. Finally, using conditional EGFR-knockout GSCs, we show that depleting EGFR increased animal survival in mice transplanted with wt-p53 GSCs.

conclusionThis study demonstrates that EGFR signaling inhibits wt-p53 function in GBM by promoting an interaction between p53 and DNA-PKcs.

Indexed as

GlioblastomaGliomaAnimalsDNADNA-Activated Protein KinaseErbB ReceptorsMicePyridazinesQuinazolinesReactive Oxygen SpeciesRNA, Small InterferingTumor Suppressor Protein p53DNADNA-Activated Protein KinaseErbB ReceptorspeposertibPyridazinesQuinazolinesReactive Oxygen SpeciesRNA, Small InterferingTumor Suppressor Protein p53DNA-PKcsEGFRglioblastomawt-p53

Identifiers

PMID35474131
PMCPMC9527520
OpenAlexW4225011983

What OpenQuestion holds

Textmetadata
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.