ArticleNature communications2026
IQGAP3 bridges matrix stiffness with glioma stem cell maintenance and radioresistance by stabilizing SOX2.
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.
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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.
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24 authors.
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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.
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