Data from: Optogenetic control of the integrated stress response limits glioblastoma invasion

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.