IκB Kinase Alpha and Cancer

I kappa B kinase alpha (Ikk-alpha) gene mutations and IKK-alpha 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-alpha 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-alpha has emerged as a tumor suppressor for SCCs. Furthermore, inducible deletion of IKK-alpha in the keratinocytes of adult mice causes spontaneous skin papillomas and carcinomas, indicating that IKK-alpha deletion functions as a tumor initiator as well as a tumor promoter. This article discusses IKK-alpha 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.