2026-08-26 カリフォルニア大学サンタバーバラ校（UCSB）
＜関連情報＞
- https://news.ucsb.edu/2026/022776/light-triggered-stress-response-suppresses-glioblastoma-spread-3d-models
- https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/cbf.70212
- https://medibio.tiisys.com/160048/
光遺伝学的手法による統合ストレス応答の制御が膠芽腫の浸潤を抑制する Optogenetic Control of the Integrated Stress Response Limits Glioblastoma Invasion
Lisa K. Månsson, Ethan Dickson, Lun Hao, Angela A. Pitenis, Maxwell Z. Wilson
Cell Biochemistry and Function Published: 15 April 2026
DOI:https://doi.org/10.1002/cbf.70212
ABSTRACT
The integrated stress response (ISR) is a highly conserved signaling network, allowing cells to adapt and respond to various stressors. With its aggressive spread and high recurrence rates, glioblastoma multiforme (GBM) is one of the toughest cancers to date, yet the role of the ISR is still to be well understood, whether activation may suppress or promote this disease, and drug-treatment of GBM has thus far shown inconclusive results. In this work, we use an optogenetic tool, opto-PKR, to specifically trigger ISR activation via light-induced oligomerizing PKR-kinases, offering high spatiotemporal and reversible control, while avoiding potential upstream damage or side effects from drugs. Using immunofluorescence and RNA-sequencing, we show that targeted ISR activation reaching levels where both adaptive (ATF4) and terminal responses (CHOP) are activated results in subsequent downregulation of genes associated with the extracellular environment and glial cell migration, further supported by ECM-stain and scratch assays. Next, we show inhibition of aggressive spread for ISR-activated GBM spheroids in collagen 3D culture. Photopatterning of ISR activation in spheroids demonstrates a cell-intrinsic effect at the tissue scale, and recovery studies indicate a tunable, non-ablative intervention space. These findings suggest a route to containment and motivate ISR-activating small molecule screening in GBM models.
Summary
- Glioblastoma is one of today’s toughest cancers with aggressive spread and high recurrence rates.
- Cellular stress response helps cells cope with difficult conditions and is involved in many diseases, but in glioblastoma, it remains unclear whether this response helps or harms the disease.
- Drug treatments in stress response studies on glioblastoma have so far shown inconclusive results.
- In light of this, we used optogenetics to specifically activate stress response using light.
- Our results show that stress response-activation inhibits glioblastoma cancer spread in tissue-like models, suggesting a new route for glioblastoma therapeutics.
