Evidence map›Paper›PMID 25601206›Full record

ArticleStem cell reports2015

EZH2 protects glioma stem cells from radiation-induced cell death in a MELK/FOXM1-dependent manner.

Sung-Hak Kim, Kaushal Joshi, Ravesanker Ezhilarasan, Toshia R Myers, Jason Siu, Chunyu Gu, Mariko Nakano-Okuno, David Taylor, Mutsuko Minata, Erik P Sulman and 4 more

Expression of concernOpen access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 107 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 1 pooled it
10.8field-weighted citation impact, top 1% 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

107 citing papers in PubMed, 1 synthesis or guideline pooled it, 175 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. m6A-TSHub: Unveiling the Context-specific mGenomics, proteomics & bioinformatics · 2023
    Article

47 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 2 countries.

Sung-Hak KimDepartment of Neurological Surgery, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Kaushal JoshiDepartment of Neurological Surgery, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Ravesanker EzhilarasanDepartment of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
Toshia R MyersBiotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
Jason SiuDepartment of Neurological Surgery, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Chunyu GuDepartment of Neurological Surgery, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Mariko Nakano-OkunoDepartment of Neurological Surgery, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
David TaylorDepartment of Neurological Surgery, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Mutsuko MinataDepartment of Neurological Surgery, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Erik P SulmanDepartment of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
Jeongwu LeeDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Krishna P L BhatDepartment of Pathology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
Anna Elisabetta SalciniBiotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
Ichiro NakanoDepartment of Neurological Surgery, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. Electronic address: ichiro.nakano@osumc.edu.
Neurological Surgery · USThe University of Texas MD Anderson Cancer Center · USThe Ohio State University · USUniversity of Copenhagen · DKCleveland Clinic Lerner College of Medicine · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Tropism Enhanced Oncolytic Adenovirus for the Treatment of Brain TumorsP50CA127001 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Juan Fueyo · 2008 to 2026
$41.2M
The Tumor Microenvironmental Barrier to Effective Viral OncolysisP01CA163205 · NCI · OHIO STATE UNIVERSITY · PI MICHAEL A CALIGIURI · 2013 to 2026
$26.0M
Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Ann E. Rougvie · 2012 to 2026
$7.5M
Metabolism Informs Intertumoral & Intratumoral HeterogeneityR01NS087913 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NAKANO, ICHIRO, RICH, JEREMY N · 2014 to 2018
$2.0M
Polycomb and Cellular Hierarchy in the BrainR01NS082312 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI LEE, JEONGWU · 2013 to 2017
$1.7M
Targeting MELK-mediated EZH2 signaling in glioma stem cellsR01NS083767 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LEE, JEONGWU, NAKANO, ICHIRO · 2013 to 2017
$1.3M
Determination of Musashi1/CD44v6 signaling in mesenchymal glioma stem cellsR21CA175875 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI NAKANO, ICHIRO, PENALVA, LUIZ OTAVIO · 2014 to 2015
$377k
NCI NIH HHS NIH/NCI P01CA163205NCI NIH HHS P01 CA163205NCI NIH HHS P50 CA127001NCI NIH HHS R21 CA175875NIH HHS P40 OD010440NIH HHS P40OD010440NINDS NIH HHS NIH/NINDS R01 NS083767NINDS NIH HHS R01 NS082312NINDS NIH HHS R01 NS083767NINDS NIH HHS R01 NS087913NINDS NIH HHS R01NS087913
6 · The paper itself

Abstract

Glioblastoma (GBM)-derived tumorigenic stem-like cells (GSCs) may play a key role in therapy resistance. Previously, we reported that the mitotic kinase MELK binds and phosphorylates the oncogenic transcription factor FOXM1 in GSCs. Here, we demonstrate that the catalytic subunit of Polycomb repressive complex 2, EZH2, is targeted by the MELK-FOXM1 complex, which in turn promotes resistance to radiation in GSCs. Clinically, EZH2 and MELK are coexpressed in GBM and significantly induced in postirradiation recurrent tumors whose expression is inversely correlated with patient prognosis. Through a gain-and loss-of-function study, we show that MELK or FOXM1 contributes to GSC radioresistance by regulation of EZH2. We further demonstrate that the MELK-EZH2 axis is evolutionarily conserved in Caenorhabditis elegans. Collectively, these data suggest that the MELK-FOXM1-EZH2 signaling axis is essential for GSC radioresistance and therefore raise the possibility that MELK-FOXM1-driven EZH2 signaling can serve as a therapeutic target in irradiation-resistant GBM tumors.

Indexed as

AnimalsCell DeathDisease Models, AnimalEnhancer of Zeste Homolog 2 ProteinGene ExpressionGene Expression Regulation, NeoplasticGliomaHeterograftsHumansMiceNeoplastic Stem CellsPolycomb Repressive Complex 2Promoter Regions, GeneticProtein BindingProtein Serine-Threonine KinasesProtein TransportEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanMELK protein, humanPolycomb Repressive Complex 2Protein Serine-Threonine Kinases

Identifiers

PMID25601206
PMCPMC4325196
OpenAlexW2116844416

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.