NF-κB-driven improvement of EHD1 contributes to erlotinib resistance in EGFR-mutant lung cancers.

ABSTRACT: Acquired resistance to epidermal growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, is a critical obstacle in the treatment of EGFR mutant-positive non-small cell lung cancer (NSCLC). EHD1, a protein of the C-terminal Eps15 homology domain-containing (EHD) family, plays a role in regulating endocytic recycling, but the mechanistic details involved in EGFR-TKI resistance and cancer stemness remain largely unclear. Here, we found that a lower EHD1 expression improved both EGFR-TKIs sensitivity, which is consistent with a lower CD133 expression, and progression-free survival in NSCLC patients. The overexpression of EHD1 markedly increased erlotinib resistance and lung cancer cell stemness in vitro and in vivo. Moreover, we demonstrated that miR-590

SUBMITTER: Wang X 

PROVIDER: S-EPMC5856828 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature