Figure 8.

Model depicting the role of PERK in mediating cellular adaptation of GSC to increasing matrix stiffness. In PERK-proficient cells, increasing matrix stiffness results in increased PERK and FLNA expression. PERK-FLNA interactions are required for F-Actin remodeling which is essential for cellular adaptation to stiffness. Phosphorylation of PERK likely facilitates FLNA interaction. This is accompanied by a change in cell morphology from round to an elongated phenotype and increased cell proliferation and migration. In PERK-deficient cells, this mechanism regulating stiffness-dependent F-Actin remodeling is disrupted, resulting in lack of morphological change and no stimulation of proliferation and migration.