PIM1 kinase promotes EMT-associated osimertinib resistance via regulating GSK3β signaling pathway in EGFR-mutant non-small cell lung cancer.

ABSTRACT: Acquired resistance is inevitable in the treatment of non-small cell lung cancer (NSCLC) with osimertinib, and one of the primary mechanisms responsible for this resistance is the epithelial-mesenchymal transition (EMT). We identify upregulation of the proviral integration site for Moloney murine leukemia virus 1 (PIM1) and functional inactivation of glycogen synthase kinase 3β (GSK3β) as drivers of EMT-associated osimertinib resistance. Upregulation of PIM1 promotes the growth, invasion, and resistance of osimertinib-resistant cells and is significantly correlated with EMT molecules expression. Functionally, PIM1 suppresses the ubiquitin-proteasome degradation of snail family transcriptional repressor 1 (SNAIL) and snail family transcriptional repressor 2 (SLUG) by deactivating GSK3β thro

SUBMITTER: Zhou J 

PROVIDER: S-EPMC11372188 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature