Clathrin-mediated EGFR endocytosis as a potential therapeutic strategy for overcoming primary resistance of EGFR TKI in wild-type EGFR non-small cell lung cancer.

ABSTRACT:

Objectives

Oncogenic alterations of epidermal growth factor receptor (EGFR) signaling are frequently noted in non-small cell lung cancer (NSCLC). In recent decades, EGFR tyrosine kinase inhibitors (TKIs) have been developed, although the therapeutic efficacy of these inhibitor is restricted to EGFR-mutant patients. In this study, we investigated that clathrin-mediated EGFR endocytosis hampers the effects of gefitinib and sustains NSCLC cells with wild-type EGFR.

Materials and methods

NSCLC cell lines (H358, Calu-3, SNU-1327, and H1703) were stimulated with the EGF and treated with gefitinib and endocytosis inhibitors (phenylarsine oxide (PAO) and Filipin III). Growth inhibition and apoptosis were evaluated. Immunofluorescence, immunoprecipitation, and western blot assay were

SUBMITTER: Kim B 

PROVIDER: S-EPMC7826488 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature