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Optogenetic Control of the Integrated Stress Response Limits Glioblastoma Invasion
Lisa K Månsson1, Ethan Dickson2, Lun Hao3
1Materials Department, University of California Santa Barbara, Santa Barbara, California, USA.
Cell Biochemistry and Function
|April 16, 2026
Summary
Activating the integrated stress response (ISR) in glioblastoma multiforme (GBM) using light controls cancer cell spread. This novel optogenetic approach offers a tunable method to potentially treat aggressive GBM tumors.
Area of Science:
- Oncology
- Cellular Biology
- Biophysics
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain cancer with high recurrence rates.
- The role of the integrated stress response (ISR) in GBM progression is not well understood.
- Current GBM drug treatments have yielded inconclusive results.
Purpose of the Study:
- To investigate the role of ISR activation in GBM.
- To develop a spatiotemporal and reversible method for ISR activation in GBM.
- To assess the impact of ISR activation on GBM cell migration and spread.
Main Methods:
- Utilized an optogenetic tool (opto-PKR) to trigger ISR activation with light.
- Employed immunofluorescence and RNA-sequencing to analyze cellular responses.
- Performed ECM-stain and scratch assays to evaluate cell migration.
- Cultured GBM spheroids in 3D collagen to assess spread inhibition.
- Used photopatterning to study ISR activation effects at the tissue scale.
Main Results:
- Targeted ISR activation downregulated genes related to the extracellular environment and glial cell migration.
- ISR activation inhibited the aggressive spread of GBM spheroids in 3D culture.
- Photopatterning demonstrated a cell-intrinsic effect of ISR activation.
- Recovery studies indicated a tunable, non-ablative intervention space.
Conclusions:
- ISR activation can suppress GBM cell migration and spread.
- Optogenetic control of ISR offers a potential therapeutic strategy for GBM.
- Findings support ISR-activating small molecule screening for GBM treatment.
