title: IκB kinase alpha and cancer.
abstract: IκB kinase alpha (Ikk-α) gene mutations and IKK-α downregulation have been detected in various human squamous cell carcinomas (SCCs), which are malignancies derived from squamous epithelial cells. These squamous epithelial cells distribute to many organs in the body; however, the epidermis is the only organ mainly composed of stratified squamous epithelial cells, called keratinocytes. SCC is the second most common type of skin cancer. Reducing IKK-α expression promotes tumor initiation, and its loss greatly enhances tumor progression from benign papillomas to malignant carcinomas during chemical skin carcinogenesis in mice. Thus, IKK-α has emerged as a tumor suppressor for SCCs. Furthermore, inducible deletion of IKK-α in the keratinocytes of adult mice causes spontaneous skin papillomas and carcinomas, indicating that IKK-α deletion functions as a tumor initiator as well as a tumor promoter. This article discusses IKK-α biological activities and associated molecular events in skin tumor development, which may provide insight into the diagnosis, treatment, and prevention of human squamous cell carcinomas (SCCs) in the future.
authors.affiliation: Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland, USA.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.forename: Zhisong
authors.initials: Z
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Yinling
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000473:pathology; D008954:Models, Biological; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology
chemical_list: D051550:I-kappa B Kinase