Transcriptomic profiling of A549 cells in response to dexamethasone, in the context of light-controlled GR degradation using novel GR-PhotoPROTACs

To enable precise modulation of GR activity, we developed photoswitchable PROTACs (PhotoPROTACs) incorporating arylazopyrazole scaffolds that allow reversible, wavelength-specific control of GR degradation. A549 lung carcinoma cells were incubated with the active (E-isomer) or inactive (Z-isomer) form of PhotoPROTAC KH-5-309 or KH-5-306 for 12 hours, with Dex added during the final 2 hours.

RNA sequencing revealed that the E-isomer of KH-5-309 selectively disrupts GR-driven dormancy-associated gene expression, while the Z-isomer remains functionally inert. This dataset provides a resource for understanding GR-mediated dormancy and demonstrates the utility of light-responsive chemical tools for spatiotemporal control of stress hormone receptor signaling to disrupt cancer cell dormancy.