A study on the senescence-inducing therapy to oral cancer by targeting IκB kinase

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We investigated the function of IκB kinase (IKK) α in oral squamous cell carcinoma (SCC).(1) At first, we examined the expressions of IKK as well as NF-κB in oral SCC tissues. IKK α is a kinase to activate NF-κB, and NF-κB is a transcription factor to transactivate anti-apoptotic genes. Thirty six biopsy specimens from patients with SCC were immunohistochemically stained. The results show that high expressions of IKKα and NF-κB p65 correlated with the invasiveness and the nodal involvement of oral SCC.(2) We caused cultured oral SCC cell line to overexpress IKKα or IKKβ by transfecting its expression vector. High levels of IKKα, but not IKKβ, inhibited the expressions of epithelial differentiation markers, involucrin and filaggrin, in SCC cells. Phorbol myristate acetate phosphorylated IKKα to inhibit the expressions of involucrin. Protein kinase C and IKKα may regulate the differentiation and senescence of SCC cells.The results described above suggest that high expressions of IKKα may contribute to the tumor survival by inhibiting the differentiation (and senescence) in SCC cells. Therefore, IKKα seems to be a therapeutic target molecule against oral cancer.