Methylation-modulated PFTK1 regulates gefitinib resistance via Wnt/β-catenin signaling in EGFR mutant non-small-cell lung cancer cells.

ABSTRACT: Inevitable gefitinib resistance is the biggest bottleneck in current treatment and the mechanisms are not fully understood. Here, we observe that PFTK1 (also named CDK14) is significantly enhanced in NSCLC with gefitinib resistance. And the upregulation of PFTK1 is negatively associated with progression-free survival (PFS) in NSCLC patients who receive gefitinib treatment. Further study suggests that gefitinib can critically accelerate PFTK1 through suppressing its promoter methylation in a DNMT3B-dependent manner. Gain and loss of function assays demonstrate that desregulation of PFTK1 significantly enhances gefitinib resistance in NSCLC. PFTK1 interacts with LRP6 and activates Wnt/β-catenin signaling to attenuate gefitinib-induced cellular apoptosis. Moreover, FMF-04-159-2, a specific co

SUBMITTER: Jia X 

PROVIDER: S-EPMC11659392 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature