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Transcriptome analysis of rigosertib resistant MDA-MB-453 cells, obtained from a CRISPR screen with WNK1 depletion.

GSE271314 Homo sapiens Expression profiling by high throughput sequencing 5 samples Submitted 2024/07/16 Platform GPL21697
Summary
In a genome-wide CRISPR-Cas9 resistance drug screen, we identified the master osmostress regulator WNK1 kinase as a modulator of the response to the mitotic drug rigosertib. Osmotic stress and WNK1 inactivation lead to an altered response not only to rigosertib but also to other microtubule-related drugs, minimizing the prototypical mitotic arrest produced by these drugs. This effect is due to an alteration in microtubule stability and polymerization dynamics, likely maintained by fluctuations in intracellular molecular crowding upon WNK1 inactivation. This promotes resistance to microtubule depolymerizing drugs, and increased sensitivity to microtubule stabilizing drugs. In summary, our data proposes WNK1 osmoregulation activity as a biomarker for microtubule-associated chemotherapy response.
Published in
Osmotic stress influences microtubule drug response via WNK1 kinase signaling
Monfort-Vengut A, Sanz-Gómez N, Ballesteros-Sánchez S et al. · Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 2025 · PMID 39855050 · doi:10.1016/j.drup.2025.101203
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Also filed as BioProject PRJNA1130914 and SRA study SRP517532. Searching any of these in the dataset finder brings you back here.

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