DUOX1 Silencing in Lung Cancer Promotes Epithelial‐to‐Mesenchymal Transition and Increased Drug Resistance

• DOI: 10.1096/fasebj.29.1_supplement.863.19
• Publication Date: 2021-06-21T17:05:54Z
• Authors: Andrew Little; Milena Hristova; Albert Vliet
• Keywords: 0303 health sciences; 03 medical and health sciences

Rationale and Objective: Dual oxidase 1 (DUOX1) is an H2O2-generating enzyme within the airway epithelium with functional roles in innate host defense epithelial homeostasis. DUOX1 suppressed lung cancers by epigenetic silencing, although its importance unknown. We used RNAi approaches to investigate impact of silencing on various molecular features cancer. Results: Stable transfection DUOX1-targeted shRNA cancer cell line H292 (H292-shDUOX1) was found result loss characteristics increased mesenchymal features, suggesting occurrence epithelial-to-mesenchymal transition (EMT). EMT has been associated enhanced resistance EGFR tyrosine kinase inhibitors (TKI) enrichment stem (CSC) populations. Indeed, H292-shDUOX1 cells are resistant TKI erlotinib display elevated expression CSC markers such as CD24high/CD44low, CD133 ALDH1. Furthermore, induction acquired or sorting subpopulations (based CD24low/CD44high) demonstrated dramatically reduced expression, further establishing close association between EMT. Conclusions Our findings indicate that promotes EMT, may thereby be strongly invasive metastatic cancer, potentially also contribute other EMT-related pathologies chronic obstructive pulmonary disease (COPD). Funding Source: NIH 5R01HL085646, UVM College Medicine