Druggable genome CRISPRi screen in 3D hydrogels reveals regulators of cortactin-driven actin remodeling in invading glioblastoma cells

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

To identify new therapeutic targets that limit glioblastoma (GBM) invasion, we applied druggable-genome CRISPR screens to patient-derived GBM cells in micro-dissectible biomimetic 3D hydrogel platforms permit separation and independent analysis of core vs. invasive fractions. We identified 12 whose suppression limited which ACP1 (LMW-PTP) Aurora Kinase B (AURKB) were validated neurosphere assays. Proximity labeling cortactin as an ACP1- AURKB link, undergoes serine phosphorylation by tyrosine dephosphorylation ACP1. Suppression or culture vivo shifted the balance reduced actin polymerization actin-cortactin co-localization. Additional biophysical implicated cell adhesion cortical stiffness, resistance mechanical stress shape plasticity needed for migration. These findings reveal a novel targetable axis balances kinase phosphatase activities regulate during invasion.

Язык: Английский

Carbohydrate polymer-driven nanoparticle synthesis and functionalization in the brain tumor therapy: A review

International Journal of Biological Macromolecules, Год журнала: 2024, Номер unknown, С. 138194 - 138194

Опубликована: Ноя. 1, 2024

Язык: Английский