Evidence map›Paper›PMID 42251046›Full record

ArticleNature communications2026

IQGAP3 bridges matrix stiffness with glioma stem cell maintenance and radioresistance by stabilizing SOX2.

Po Zhang, Weichi Wu, Tengfei Huang, Xujia Wu, Donghai Wang, Huairui Yuan, Suchet Taori, Fanen Yuan, Frank P Vendetti, Rui Wang and 14 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

24 authors.

Po Zhang *UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Weichi Wu *UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Tengfei HuangUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Xujia WuUPMC Hillman Cancer Center, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-6904-0778
Donghai WangUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Huairui YuanUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Suchet TaoriUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Fanen YuanUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Frank P VendettiDepartment of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Rui WangUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Tingting DuanUPMC Hillman Cancer Center, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-4482-5587
Hailong MiUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Huan LiUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Kailin YangDepartment of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa, IA, USA.
Daqi LiUPMC Hillman Cancer Center, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-7448-7435
Ahmed HabibUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Briana C PragerDepartment of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
Ryan C GimpleDepartment of Medical Oncology, Washington University in Saint Louis, Saint Louis, MO, USA.ORCID http://orcid.org/0000-0002-7189-3243
Pascal O ZinnUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Kalil AbdullahUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Christopher BakkenistUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Junran ZhangDepartment of Radiation Oncology, The Ohio State University Comprehensive Cancer Center and College of Medicine, Columbus, OH, USA.ORCID http://orcid.org/0000-0001-5413-3675
Qiulian WuUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Jeremy N RichUPMC Hillman Cancer Center, Pittsburgh, PA, USA. drjeremyrich@gmail.com.ORCID http://orcid.org/0000-0001-7845-5302

Funding

Metabolic Regulation of Glioblastoma EpitranscriptomicsR01CA268634 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Sameer Agnihotri, JEREMY N RICH · 2022 to 2026
$2.9M
Targeting the Circadian Rhythm in Glioblastoma Stem Cells (R01CA238662)R01CA238662 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KAY, STEVE A, RICH, JEREMY N · 2020 to 2024
$2.8M
Targeting Glioblastoma Stem CellsR35CA283998 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JEREMY N RICH · 2024 to 2026
$1.9M
Metabolic Control of Translation in GlioblastomaR01NS136424 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Sameer Agnihotri, JEREMY N RICH · 2024 to 2026
$1.7M
Targeting Amino Acid Metabolism in GlioblastomaR01NS134724 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Kalil G Abdullah, JEREMY N RICH · 2024 to 2026
$1.7M
Dual Targeting of Brain Tumor Initiating Cells through Inhibition of BMI1 and EZH2 (R01NS103434)R01NS103434 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI RICH, JEREMY N · 2017 to 2021
$1.7M
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) CA238662Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) CA268634Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) CA283998Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) NS103434Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) NS134724Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) NS136424NCI NIH HHS R01 CA238662NCI NIH HHS R01 CA268634NCI NIH HHS R35 CA283998NINDS NIH HHS R01 NS103434NINDS NIH HHS R01 NS134724NINDS NIH HHS R01 NS136424United States Department of Defense | Defense Health Agency (DHA) HT9425-23-1-0689
6 · The paper itself

Abstract

Drivers of therapeutic resistance in cancer include evolving tumor cell heterogeneity and the tumor microenvironment (TME). We find that increased matrix stiffness promotes radioresistance in glioblastoma (GBM) and maintains tumor cell hierarchies. Differential gene expression reveals that stiff matrices induce expression of IQGAP3 (IQ Motif Containing GTPase Activating Protein 3) through YAP1 and TEAD transcription factors in GBM stem cells (GSCs). IQGAP3 promotes GSC self-renewal and survival upon radiation treatment through binding and stabilization of core stem cell transcription factor, SOX2. Targeting IQGAP3 reduces SOX2 protein levels in vitro and in vivo, increasing GSC radiosensitivity and inhibiting tumor growth. Structure-function drug screening of FDA-approved agents blocking IQGAP3-SOX2 binding identifies trimetrexate as a brain penetrant pharmacologic disruptor of IQGAP3 function in radioresistance, sensitizing GSCs to radiotherapy. These results identify molecular underpinnings for biomechanical promotion of cancer stem cell maintenance and therapeutic resistance, informing therapeutic strategies to augment efficacy of radiotherapy.

Indexed as

Brain NeoplasmsGlioblastomaGliomaNeoplastic Stem CellsRadiation ToleranceSOXB1 Transcription FactorsAdaptor Proteins, Signal TransducingAnimalsCell Line, TumorExtracellular MatrixGene Expression Regulation, NeoplasticHumansMiceTranscription FactorsTumor MicroenvironmentYAP-Signaling ProteinsAdaptor Proteins, Signal TransducingSOX2 protein, humanSOXB1 Transcription FactorsTranscription FactorsYAP1 protein, humanYAP-Signaling Proteins

Identifiers

PMID42251046
PMCPMC13396378

What OpenQuestion holds

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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.