Evidence map›Paper›PMID 36732025›Full record

ArticleGenes & development2023

WDR5 represents a therapeutically exploitable target for cancer stem cells in glioblastoma.

Kelly Mitchell, Samuel A Sprowls, Sonali Arora, Sajina Shakya, Daniel J Silver, Christopher M Goins, Lisa Wallace, Gustavo Roversi, Rachel E Schafer, Kristen Kay and 15 more

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.

  1. Pooled it
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  8. Review
  9. Probing the Cancer Mutational Landscape of KMT2 Regulatory Subunits.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
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  15. Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025
    Review
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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

25 authors at 6 institutions in 1 country.

Kelly MitchellDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA.ORCID 0000-0002-1124-7864
Samuel A Sprowls *Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA.
Sonali Arora *Human Biology Division, Fred Hutchinson Cancer Center, Seattle, Washington 98109, USA.
Sajina ShakyaDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA.
Daniel J SilverDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA.
Christopher M GoinsCenter for Therapeutics Discovery, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA; lathiaj@ccf.org christopher.hubert@case.edu.
Lisa WallaceDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA.
Gustavo RoversiDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA.
Rachel E SchaferDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA.
Kristen KayDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA.
Tyler E MillerDepartment of Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Adam LaukoDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA.
John BassettHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, Washington 98109, USA.
Anjali KashyapDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA.
Jonathan D'Amato KassDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA.
Erin E Mulkearns-HubertDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA.
Sadie JohnsonDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA.
Joseph AlvaradoCenter for Therapeutics Discovery, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA.
Jeremy N RichUniversity of Pittsburgh Medical Center Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Eric C HollandHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, Washington 98109, USA.
Patrick J PaddisonHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, Washington 98109, USA.
Anoop P PatelHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, Washington 98109, USA.
Shaun R Stauffer *Center for Therapeutics Discovery, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA.
Christopher G Hubert *Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA.
Justin D Lathia *Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44106, USA; lathiaj@ccf.org christopher.hubert@case.edu.
Cleveland Clinic Lerner College of Medicine · USFred Hutch Cancer Center · USCleveland Clinic · USMassachusetts General Hospital · USUniversity of Washington · USUPMC Hillman Cancer Center · US

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR002548 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI MCCOMSEY, GRACE A · 2018 to 2022
$35.5M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
Vanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ALVIN C POWERS · 2012 to 2026
$29.3M
Sex-specific differences in the tumor microenvironment alter glioblastoma growthP01CA245705 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI Justin D. Lathia · 2020 to 2026
$15.0M
Institutional Career Development CoreKL2TR002547 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI DWEIK, RAED A. · 2018 to 2022
$7.7M
The role and mechanism of alternative RNA splice variants and gene fusions as drivers of cancerR35CA253119 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric C. Holland · 2021 to 2026
$6.5M
Dynamic Complexity of Brain Tumor Stem Cells (R35CA197718)R35CA197718 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI RICH, JEREMY N · 2015 to 2021
$6.4M
RESEARCH ONCOLOGY TRAINING GRANTT32CA059366 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI JACKSON, MARK W. · 1993 to 2025
$5.5M
Contribution of Myeloid-Derived Suppressor Cells to Neuro-Inflammatory Alterations and Disease Progression in GlioblastomaR35NS127083 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI Justin D. Lathia · 2022 to 2026
$3.1M
Sex Differences in Blood-Brain and Blood-Tumor Barrier Dynamics in GlioblastomaK00CA253768 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SPROWLS, SAMUEL ADAM TYLER · 2022 to 2024
$281k
Role of SerpinB3 in glioblastoma cancer stem cellsF30CA250254 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI LAUKO, ADAM · 2021 to 2024
$191k
Effects of the metalloproteinase ADAMDEC1 in glioblastoma-associated myeloid cellsF32NS116109 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI MITCHELL, KELLY · 2020 to 2020
$65k
NCATS NIH HHS KL2 TR002547NCATS NIH HHS UL1 TR002548NCI NIH HHS F30 CA250254NCI NIH HHS K00 CA253768NCI NIH HHS P01 CA245705NCI NIH HHS R35 CA197718NCI NIH HHS R35 CA253119NCI NIH HHS T32 CA059366NIDDK NIH HHS P30 DK020593NIGMS NIH HHS T32 GM007250NINDS NIH HHS F32 NS116109NINDS NIH HHS R35 NS127083
6 · The paper itself

Abstract

Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors driven by populations of cancer stem cells (CSCs). However, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy-resistant niche and identified WDR5 as indispensable for this population. WDR5 is a component of the WRAD complex, which promotes SET1 family-mediated Lys4 methylation of histone H3 (H3K4me), associated with positive regulation of transcription. In GBM CSCs, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, including the POU5F1(OCT4)::SOX2 motif. Use of a SOX2/OCT4 reporter demonstrated that WDR5 inhibitor treatment diminished cells with high reporter activity. Furthermore, WDR5 inhibitor treatment and WDR5 knockdown altered the stem cell state, disrupting CSC in vitro growth and self-renewal, as well as in vivo tumor growth. These findings highlight the role of WDR5 and the WRAD complex in maintaining the CSC state and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers.

Indexed as

GlioblastomaHistone-Lysine N-MethyltransferaseHumansIntracellular Signaling Peptides and ProteinsNeoplastic Stem CellsTranscription FactorsHistone-Lysine N-MethyltransferaseIntracellular Signaling Peptides and ProteinsTranscription FactorsWDR5 protein, humanepigeneticsglioblastomastem cell

Identifiers

PMID36732025
PMCPMC10069451
OpenAlexW4318985518

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.