Article ID Journal Published Year Pages File Type
2108097 Cancer Cell 2013 14 Pages PDF
Abstract

SummaryHere, 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. IKKαlowK5+p63hi 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 IKKαlowK5+p63hi 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.

► We establish a robust mouse lung SCC model that resembles human lung SCCs ► IKKα reduction deregulates oncogenes, tumor suppressors, and stem cell genes ► Increased IKKα mutant macrophages promote the initiation of lung SCCs ► IKKα prevents the abnormality of squamous cells in multiple epithelial organs

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Life Sciences Biochemistry, Genetics and Molecular Biology Cancer Research
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