PT - JOURNAL ARTICLE AU - Stéphane Renaud AU - Dominique Guenot AU - Pierre-Emmanuel Falcoz AU - Gilbert Massard AU - Michèle Beau-Faller TI - Role of hypoxia in epithelial-to-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) DP - 2014 Sep 01 TA - European Respiratory Journal PG - P814 VI - 44 IP - Suppl 58 4099 - http://erj.ersjournals.com/content/44/Suppl_58/P814.short 4100 - http://erj.ersjournals.com/content/44/Suppl_58/P814.full SO - Eur Respir J2014 Sep 01; 44 AB - Introduction : Non small cell lung cancer (NSCLC) remains the first cause of cancer-related death worldwide, mainly because of treatment resistance and late diagnosis. Epithelial-to-mesenchymal transition (EMT) is linked with tumor progression and drug resistance in many cancers. Our aim was to evaluate in vitro if hypoxia, could induce EMT on NSCLC. Material and methods : Our work is performed on 2 EGFR mutated NSCLC cell lines (H1650 cell line : exon 19 deletion, H1975 cell line : L858R and T790M mutations). We studied in normoxia (21% O2) and hypoxia (1% O2) conditions of culture : cells morphology, proliferative and migrative capacities, HIF-1αexpression, protein and mRNA expression of epithelial (E-cadherin) and mesenchymal (vimentine) markers, as well as EMT transcription factors (ZEB-1, Snail-1, Snail-2, Twist-1 and Twist-2). Results : Hypoxia leads to a fibroblastoïd morphology in both cell lines. Proportion of migrated cells is significantly higher in hypoxia in both cell lines H1650 and H1975 (p<0.001). Expression of HIF-1αincreases in hypoxia, associated with a decrease of the expression of E-cadherin with a cytoplasmic translocation, and an increase in vimentin expression in both cells. Expression of the EMT-transcription factors increases in hypoxia in both cells. Experiments with HIF-1a SiRNa show that over-expression of EMT-transcription factors is lost when HIF-1αis inhibited. Conclusion : Hypoxia seems to induce a partial EMT phenotype in NSCLC cell lines harboring EGFR mutation, in part related to HIF-1α expression.