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Updated: Apr 22, 2026

Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
Published on: July 30, 2020
Aurora-A drives sorafenib resistance by scaffolding stress granule assembly via phase separation
Lingyu Kong1, Fumei Zhong2,3, Fazhi Yu1
1Department of Digestive disease, The First Affiliated Hospital of University of Science and Technology of China (USTC), State Key Laboratory of Immune Response and Immunotherapy, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
Abstract:
The mitotic kinase Aurora-A is frequently overexpressed in cancers and contributes to tumor progression and therapy resistance, yet the mechanisms underlying its role in drug resistance remain unclear. Here, we show that sorafenib treatment triggers Aurora-A phase separation, leading to its recruitment into stress granules (SGs), membraneless organelles that promote cancer cell survival. Aurora-A facilitates robust SGs assembly, thereby conferring sorafenib resistance. Mechanistically, upon sorafenib-induced SGs formation, Aurora-A binds RNA via positively charged lysine/arginine residues within its intrinsically disordered region (IDR). Mutating these K/R residues with IDR of Aurora-A disrupts its RNA binding, impairs SGs assembly, and resensitizes cancer cells to sorafenib. Together, our work identifies Aurora-A as a kinase-activity-independent, RNA-binding scaffold essential for stress-adaptive biomolecular condensation, revealing a druggable phase-separation axis distinct from canonical Aurora-A kinase signaling.
Insights
Aurora-A kinase promotes cancer cell survival by forming stress granules during sorafenib treatment. Disrupting its RNA binding resensitizes cells to this cancer drug.
Area of Science:
- Molecular Biology
- Cancer Biology
- Biochemistry
Background:
- Aurora-A kinase is overexpressed in cancers, contributing to tumor progression and therapy resistance.
- The precise mechanisms linking Aurora-A to drug resistance are not fully understood.
Purpose of the Study:
- To investigate the role of Aurora-A in sorafenib resistance.
- To elucidate the molecular mechanisms by which Aurora-A contributes to drug resistance.
Main Methods:
- Studied the effect of sorafenib treatment on Aurora-A localization and function.
- Investigated Aurora-A's interaction with RNA and stress granules (SGs).
- Utilized site-directed mutagenesis to assess the importance of specific Aurora-A residues.
Main Results:
- Sorafenib treatment induces Aurora-A phase separation and recruitment into stress granules.
- Aurora-A promotes stress granule assembly, conferring resistance to sorafenib.
- Aurora-A binds RNA via its intrinsically disordered region (IDR), a process crucial for SG formation and drug resistance.
Conclusions:
- Aurora-A acts as an RNA-binding scaffold, independent of its kinase activity, to facilitate stress-adaptive biomolecular condensation.
- Targeting the phase-separation properties of Aurora-A offers a novel therapeutic strategy distinct from inhibiting its kinase signaling.
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