Lifespan assays were performed at room temperature and survival was scored every 2�C4 days as the ability tomove in response to touch with a platinum wire. 200 mM FUDR was used in lifespan assays to prevent progeny production, except for experiments with fem-1 hermaphrodites, which are sterile and do not produce progeny . FUDR is also bacteriocidal and bacteriostatic. Maximum lifespan was SCH772984 ERK inhibitor calculated by the mean lifespan of the oldest 10% cohort in each experiment. Log-Rank P-values within experiments were calculated using the Survival/Reliability function in JMP 5.0.1.2 . Significance probability P-values over multiple experiments with the same conditions were calculated with the GLM Procedure in SAS 9.2 , with treatment and experiment number as the two independent factors for two-way ANOVA, and days of life as the dependent variable. Keratinocytes of the basal layer of the epidermis are mitotic, providing new cells to replace those that are shed. After moving to the suprabasal layers, the cells gradually differentiate and give rise to the cornified layer at the surface of the skin that protects the internal organs. Therefore, a balance between keratinocyte proliferation and differentiation is required to maintain epidermal homeostasis. IKKa is a fundamental component of the IKK complex that regulates the NF-kB signalling pathway . IKKa has a fundamental role in regulating keratinocyte proliferation and differentiation . The epidermis of IKKa2/2 newborn mice lacks a terminally differentiated cornified layer and exhibits marked thickening . Reintroduction of IKKa or a kinase-inactive mutant IKKa induces terminal differentiation of keratinocyte and represses hyperproliferation . This demonstrates that IKKa is buy GDC-0941 necessary for epidermal differentiation independently of its kinase activity . We have described that IKKa increases the differentiation of human keratinocytes by a mechanism dependent on E-cadherin . Other adhesion molecules such as claudin-23, occludin and desmoglein 3 have also been found to be regulated by IKKa and to play a role in epidermal terminal differentiation and skin barrier function . Non melanoma skin cancer is the most common malignancy in humans: BCCs and SCCs represent the vast majority of the tumors diagnosed. The incidence of both benign and malignant NMSC has been rising at an alarming rate for the past several years. The role of IKKa in cancer development remains controversial: while it has been suggested that it functions as a tumor suppressor in skin cancer , there are also evidences that support a role of IKKa as promoter of cancer progression and metastasis in different types of neoplasias such as breast cancer , hepatocarcinomas , prostate cancer and colorectal cancer .