Year: 2018
Type: article
Abstract: While many studies have demonstrated that canonical NF-κB signaling is a central pathway in lung tumorigenesis, the role of non-canonical NF-κB signaling in lung cancer remains undefined. We observed frequent nuclear accumulation of the non-canonical NF-κB component p100/p52 in human lung adenocarcinoma. To investigate the impact of non-canonical NF-κB signaling on lung carcinogenesis, we employed transgenic mice with doxycycline-inducible expression of p52 in airway epithelial cells. p52 over-expression led to increased tumor number and progression after injection of the carcinogen urethane. Gene expression analysis of lungs from transgenic mice combined with in vitro studies suggested that p52 promotes proliferation of lung epithelial cells through regulation of cell cycle-associated genes. Using gene expression and patient information from The Cancer Genome Atlas (TCGA) database, we found that expression of p52-associated genes was increased in lung adenocarcinomas and correlated with reduced survival, even in early stage disease. Analysis of p52-associated gene expression in additional human lung adenocarcinoma datasets corroborated these findings. Together, these studies implicate the non-canonical NF-κB component p52 in lung carcinogenesis and suggest modulation of p52 activity and/or downstream mediators as new therapeutic targets.
Source: Scientific Reports
Language: English
Topic: NF-κB Signaling Pathways
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: U.S. Department of Veterans Affairs, Vanderbilt University, Georgia Clinical and Translational Science Alliance, National Institutes of Health, National Eye Institute, National Cancer Institute, National Center for Research Resources, H2020 European Research Council, FP7 Ideas: European Research Council
Awards: G1344704808, G1352196292, G1812229208, G2043477120, G2307883750, The Vanderbilt Institute for Clinical and Translational Research (VICTR) UL1, G338527938, G3433274139, G4512720654, G563474107, G5853943267, G5988535313, Supplying lung adenocarcinoma cell lines to the cancer research community., G7220527126, G725763919, VANTAGE:Consolidation to create the Vanderbilt Technologies for Advanced Genomics, G8543375580, G9000023717, G9000060478, G9000081609, G9000083539, G9000127534, G9000300101, G949362299, KRas mutation interactions with host immunity in malignant pleural effusion, G95732390
OpenAlex ID: W2807688681