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

• DOI: 10.1038/s41419-018-0447-7
• Publication Date: 2018-04-04T02:27:41Z
• Authors: Xiaoyuan Wang; Hang Yin; Hongxia Zhang; Jing Hu; Hailing Lu; Chunhong Li; Mengru Cao; Shi Yan; Li Cai
• Keywords: Erlotinib Hydrochloride

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, protein C-terminal Eps15 homology domain-containing (EHD) family, plays role regulating endocytic recycling, but mechanistic details involved EGFR-TKI stemness remain largely unclear. Here, we found that lower EHD1 expression improved both EGFR-TKIs sensitivity, which consistent with CD133 expression, progression-free survival NSCLC patients. The overexpression markedly increased erlotinib vitro vivo. Moreover, demonstrated miR-590 targeted 3′-UTR was regulated by NK-κB, resulting downregulated sensitivity repressed stem-like properties We an important phenotype cancer, these results suggest targeting NF-κB/miR-590/EHD1 pathway has potential therapeutic promise EGFR-mutant patients acquired resistance.