PXD072748

PXD072748 is an original dataset announced via ProteomeXchange.

Title	IQGAP3 bridges matrix stiffness with glioma stem cell maintenance and radioresistance by stabilizing SOX2
Description	Drivers of therapeutic resistance in cancer include evolution of tumor cell heterogeneity and the tumor microenvironment (TME). Here, we found that increased matrix stiffness promotes radioresistance in glioblastoma (GBM) and maintains the tumor cell hierarchy. Differential gene expression revealed that stiff matrices induced expression of IQGAP3 (IQ Motif Containing GTPase Activating Protein 3) specifically in GBM stem cells (GSCs). IQGAP3 promoted GSC self-renewal and survival upon radiation treatment through binding and stabilization of the core stem cell transcription factor, SOX2. Targeting IQGAP3 reduced 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 binding to SOX2 identified trimetrexate as a brain penetrant pharmacologic disruptor of IQGAP3 function in radioresistance, sensitizing GSCs to radiotherapy. Our results identify molecular underpinnings for biomechanical promotion of cancer stem cell maintenance and therapeutic resistance, informing a therapeutic strategy to augment efficacy of radiotherapy.
HostingRepository	PRIDE
AnnounceDate	2026-02-11
AnnouncementXML	Submission_2026-02-11_07:23:05.856.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Weichi Wu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Bruker TDF format

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-07 02:23:40	ID requested
⏵ 1	2026-02-11 07:23:06	announced

Dataset with its publication pending

submitter keyword: cancer stem cell, glioma stem cell,glioblastoma, radiation, matrix stiffness, IQGAP3, SOX2

Jeremy Rich
contact affiliation	1. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA 2. UPMC Hillman Cancer Center, Pittsburgh, PA, USA 3. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA 4. Department of Neurology, University of North Carolina, Chapel Hill, NC, USA (lab head)
contact email	drjeremyrich@gmail.com
lab head
Weichi Wu
contact affiliation	Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
contact email	wuweichi@hotmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/02/PXD072748

PRIDE project URI

• PRIDE
  1. PXD072748
     1. Label: PRIDE project
     2. Name: IQGAP3 bridges matrix stiffness with glioma stem cell maintenance and radioresistance by stabilizing SOX2