Cytoskeletal remodeling via CAMSAP3 downregulation drives resistance to osimertinib in NSCLC cells.

ABSTRACT: Osimertinib, also known as AZD9291, is a highly potent and selective EGFR mutants (including exon 19 deletion, L858R/T790M) inhibitor that significantly inhibits EGFR phosphorylation signaling. However, acquired resistance to osimertinib is inevitable in the treatment of non-small cell lung cancer (NSCLC). Microtubules, key cytoskeletal components involved in intracellular cargo transport, mediate EGFR-endosomal recycling, yet their specific role in osimertinib resistance remains to be elucidated. In this study, we found that centrosomal microtubule formation was increased in osimertinib-resistant NSCLC cells, and calmodulin-regulated spectrin-associated protein 3 (CAMSAP3) was identified as the key molecule responsible for the change of microtubule morphology. Genetic modulation via CAMSA

SUBMITTER: Yang F 

PROVIDER: S-EPMC12830379 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature