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Publication : IKKalpha is required to maintain skin homeostasis and prevent skin cancer.

First Author  Liu B Year  2008
Journal  Cancer Cell Volume  14
Issue  3 Pages  212-25
PubMed ID  18772111 Mgi Jnum  J:141162
Mgi Id  MGI:3817360 Doi  10.1016/j.ccr.2008.07.017
Citation  Liu B, et al. (2008) IKKalpha is required to maintain skin homeostasis and prevent skin cancer. Cancer Cell 14(3):212-25
abstractText  It has long been known that excessive mitotic activity due to H-Ras can block keratinocyte differentiation and cause skin cancer. It is not clear whether there are any innate surveillants that are able to ensure that keratinocytes undergo terminal differentiation, preventing the disease. IKKalpha induces keratinocyte terminal differentiation, and its downregulation promotes skin tumor development. However, its intrinsic function in skin cancer is unknown. Here, we found that mice with IKKalpha deletion in keratinocytes develop a thickened epidermis and spontaneous squamous cell-like carcinomas. Inactivation of epidermal growth factor receptor (EGFR) or reintroduction of IKKalpha inhibits excessive mitosis, induces terminal differentiation, and prevents skin cancer through repressing an EGFR-driven autocrine loop. Thus, IKKalpha serves as an innate surveillant.
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