TY - JOUR T1 - CHUK/IKK-α loss in lung epithelial cells enhances NSCLC growth associated with HIF up-regulation JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900460 VL - 2 IS - 6 SP - e201900460 AU - Evangelia Chavdoula AU - David M Habiel AU - Eugenia Roupakia AU - Georgios S Markopoulos AU - Eleni Vasilaki AU - Antonis Kokkalis AU - Alexander P Polyzos AU - Haralabia Boleti AU - Dimitris Thanos AU - Apostolos Klinakis AU - Evangelos Kolettas AU - Kenneth B Marcu Y1 - 2019/12/01 UR - https://www.life-science-alliance.org/content/2/6/e201900460.abstract N2 - Through the progressive accumulation of genetic and epigenetic alterations in cellular physiology, non–small-cell lung cancer (NSCLC) evolves in distinct steps involving mutually exclusive oncogenic mutations in K-Ras or EGFR along with inactivating mutations in the p53 tumor suppressor. Herein, we show two independent in vivo lung cancer models in which CHUK/IKK-α acts as a major NSCLC tumor suppressor. In a novel transgenic mouse strain, wherein IKKα ablation is induced by tamoxifen (Tmx) solely in alveolar type II (AT-II) lung epithelial cells, IKKα loss increases the number and size of lung adenomas in response to the chemical carcinogen urethane, whereas IKK-β instead acts as a tumor promoter in this same context. IKKα knockdown in three independent human NSCLC lines (independent of K-Ras or p53 status) enhances their growth as tumor xenografts in immune-compromised mice. Bioinformatics analysis of whole transcriptome profiling followed by quantitative protein and targeted gene expression validation experiments reveals that IKKα loss can result in the up-regulation of activated HIF-1-α protein to enhance NSCLC tumor growth under hypoxic conditions in vivo. ER -