AHSA1-HSP90AA1 complex stabilized IFI6 and TGFB1 promotes mitochondrial stability and EMT in EGFR-mutated lung adenocarcinoma under Osimertinib pressure.

ABSTRACT: Tyrosine kinase inhibitors (TKIs) have substantially improved the management of lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations, however, not all patients can derive benefit from it. We found that the overexpression of IFI6 under the influence of the AHSA1-HSP90AA1 complex significantly enhances Osimertinib resistance in EGFR-mutated lung adenocarcinoma cells. This effect is achieved by stabilizing mitochondrial function, reducing apoptosis, and promoting cell survival pathways via increased Akt phosphorylation. Additionally, we revealed that TGFB1 further promotes epithelial-mesenchymal transition (EMT) and enhances the invasive and migratory capabilities of these cells, thereby intensifying resistance. Regarding mechanisms, the AHSA1-HSP90AA1 complex stabi

SUBMITTER: Sui Y 

PROVIDER: S-EPMC12000569 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature