Hypoxia Promotes Resistance to EGFR Inhibition in NSCLC Cells via the Histone Demethylases, LSD1 and PLU-1.

ABSTRACT: The development of small-molecule tyrosine kinase inhibitors (TKI) specific for epidermal growth factor receptors (EGFR) with activating mutations has led to a new paradigm in the treatment of non-small cell lung cancer (NSCLC) patients. However, most patients eventually develop resistance. Hypoxia is a key microenvironmental stress in solid tumors that is associated with poor prognosis due, in part, to acquired resistance to conventional therapy. This study documents that long-term, moderate hypoxia promotes resistance to the EGFR TKI, gefitinib, in the NSCLC cell line HCC827, which harbors an activating EGFR mutation. Following hypoxic growth conditions, HCC827 cells treated with gefitinib upregulated N-cadherin, fibronectin, and vimentin expression and downregulated E-cadherin, characte

SUBMITTER: Lu Y 

PROVIDER: S-EPMC6170700 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature