Primary cilia promote resistance to EGFR tyrosine kinase inhibitor, osimertinib, in non-small cell lung cancer - PubMed
5 hours ago
- #non-small cell lung cancer
- #osimertinib resistance
- #primary cilia
- Primary cilia formation is linked to resistance to osimertinib in non-small cell lung cancer (NSCLC).
- Osimertinib-resistant NSCLC cells show increased cilia formation, α-tubulin acetylation, and reduced HDAC6 activity.
- HDAC6 inhibition increases cilia formation in osimertinib-sensitive cells, while HDAC6 overexpression sensitizes resistant cells to osimertinib.
- Knocking down IFT88, essential for cilia formation, reverses osimertinib resistance in mouse models.
- Sodium influx during EGFR inhibition promotes cilia formation via HDAC6 inactivity and α-tubulin acetylation.
- Inhibiting sodium influx with dibutyryl-cAMP reduces cilia formation, increases osimertinib sensitivity, and slows tumor progression in mice.