What does this research mean for the field?

Matrix stiffness drives radioresistance in glioblastoma through YAP1/TEAD-mediated upregulation of IQGAP3, which stabilizes SOX2 to maintain cancer stem cells, an interaction that can be pharmacologically disrupted by trimetrexate to restore radiosensitivity. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research investigates how matrix stiffness influences glioma stem cell maintenance and radioresistance through IQGAP3 and SOX2.

June 8, 2026Nature CommunicationsOpen Access

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

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This research investigates how matrix stiffness influences glioma stem cell maintenance and radioresistance through IQGAP3 and SOX2.
Differential gene expression analyses were conducted to assess the effect of matrix stiffness on IQGAP3 expression.
In vitro and in vivo experiments were performed targeting IQGAP3 to evaluate its role in radiosensitivity of glioma stem cells.
Structure-function drug screening identified trimetrexate as a disruptor of IQGAP3-SOX2 binding.
Increased matrix stiffness led to higher IQGAP3 expression and enhanced SOX2 stability, promoting glioma stem cell survival after radiation.
Blocking IQGAP3 resulted in decreased SOX2 levels, enhancing glioma stem cell radiosensitivity and reducing tumor growth.
Trimetrexate effectively disrupted IQGAP3 function, sensitizing glioma stem cells to radiotherapy.

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Implication

Randomized trial shows matrix stiffness affects radioresistance in glioblastoma, suggesting new therapies could improve treatment outcomes.

Cite This Study

Zhang et al. (2026) studied this question.

synapsesocial.com/papers/6a265cffad53cfb9357c63ac https://doi.org/10.1038/s41467-026-74058-0

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Implication

Randomized trial shows matrix stiffness affects radioresistance in glioblastoma, suggesting new therapies could improve treatment outcomes.

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

Key Points

Discussion

Implication

Cite This Study

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

Key Points

Discussion

Implication

Cite This Study

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