Nature Communications, Published online: 06 June 2026; doi:10.1038/s41467-026-74058-0 In glioblastoma, matrix stiffness has been linked to poor prognosis and resistance to therapy. Here, the authors demonstrate that matrix stiffness drives radioresistance via upregulation of IQGAP3 promoting cancer cell stemness via SOX2 stabilization and show that blocking this interaction resensitises glioblastoma cells to radiotherapy.