The pivotal role of IKKα in the development of spontaneous lung squamous cell carcinomas.
Cancer Cell, 2013/4/15;23(4):527-40.
Xiao Z[1], Jiang Q, Willette-Brown J, Xi S, Zhu F, Burkett S, Back T, Song NY, Datla M, Sun Z, Goldszmid R, Lin F, Cohoon T, Pike K, Wu X, Schrump DS, Wong KK, Young HA, Trinchieri G, Wiltrout RH, Hu Y
Affiliations
PMID: 23597566
Impact factor: 38.585
Abstract
Here, we report that kinase-dead IKKα knockin mice develop spontaneous lung squamous cell carcinomas (SCCs) associated with IKKα downregulation and marked pulmonary inflammation. IKKα reduction upregulated the expression of p63, Trim29, and keratin 5 (K5), which serve as diagnostic markers for human lung SCCs. IKKα(low)K5(+)p63(hi) cell expansion and SCC formation were accompanied by inflammation-associated deregulation of oncogenes, tumor suppressors, and stem cell regulators. Reintroducing transgenic K5.IKKα, depleting macrophages, and reconstituting irradiated mutant animals with wild-type bone marrow (BM) prevented SCC development, suggesting that BM-derived IKKα mutant macrophages promote the transition of IKKα(low)K5(+)p63(hi) cells to tumor cells. This mouse model resembles human lung SCCs, sheds light on the mechanisms underlying lung malignancy development, and identifies targets for therapy of lung SCCs.
MeSH terms
Animals; Carcinoma, Squamous Cell; Cell Differentiation; Cell Growth Processes; Cell Line, Tumor; Cell Transformation, Neoplastic; Disease Models, Animal; Gene Expression Regulation, Neoplastic; Humans; I-kappa B Kinase; Lung Neoplasms; Mice; Mice, Transgenic; Phosphoproteins; Trans-Activators; Transcription Factors
More resources
Full text:
Europe PubMed Central; PubMed Central
EndNote: Download