Activating NEDD4L suppresses EGFR-driven lung adenocarcinoma growth via facilitating EGFR proteasomal degradation.

ABSTRACT:

Background

Resistant mutations and amplification of the epidermal growth factor receptor (EGFR), followed by the upregulation of its translated protein undermines the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung adenocarcinoma (LUAD). This underscores that promoting EGFR protein degradation may be a promising strategy for treatment.

Methods

Ubiquitin ligases database analysis identified NEDD4L as a mediator of EGFR proteasomal degradation, which was further confirmed by qPCR, western blot, immunofluorescence staining and CO-IP. The upstream regulatory role of FOXM1 on NEDD4L was elucidated through bioinformatics analyses and validated using dual luciferase reporter assay, ChIP, qPCR, western blot and immunohistochemistry. Virtual screening and molec

SUBMITTER: Chen M 

PROVIDER: S-EPMC12541971 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature