RT Journal Article SR Electronic 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 FD Life Science Alliance LLC SP e201900460 DO 10.26508/lsa.201900460 VO 2 IS 6 A1 Chavdoula, Evangelia A1 Habiel, David M A1 Roupakia, Eugenia A1 Markopoulos, Georgios S A1 Vasilaki, Eleni A1 Kokkalis, Antonis A1 Polyzos, Alexander P A1 Boleti, Haralabia A1 Thanos, Dimitris A1 Klinakis, Apostolos A1 Kolettas, Evangelos A1 Marcu, Kenneth B YR 2019 UL http://www.life-science-alliance.org/content/2/6/e201900460.abstract 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.