PT - JOURNAL ARTICLE AU - Chavdoula, Evangelia AU - Habiel, David M AU - Roupakia, Eugenia AU - Markopoulos, Georgios S AU - Vasilaki, Eleni AU - Kokkalis, Antonis AU - Polyzos, Alexander P AU - Boleti, Haralabia AU - Thanos, Dimitris AU - Klinakis, Apostolos AU - Kolettas, Evangelos AU - Marcu, Kenneth B TI - CHUK/IKK-α loss in lung epithelial cells enhances NSCLC growth associated with HIF up-regulation AID - 10.26508/lsa.201900460 DP - 2019 Dec 01 TA - Life Science Alliance PG - e201900460 VI - 2 IP - 6 4099 - http://www.life-science-alliance.org/content/2/6/e201900460.short 4100 - http://www.life-science-alliance.org/content/2/6/e201900460.full SO - Life Sci. Alliance2019 Dec 01; 2 AB - 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.