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.