Lip squamous cell carcinoma (LSCC) may develop from a potentially malignant disorder known as Actinic cheilitis (AC). The p21-activated kinases (PAKs) are possible targets for cancer therapeutics. The LSSC and AC samples were analyzed by immunohistochemistry in order to detects endogenous levels PAKs group I (PAK1 and PAK2) and group II (PAK4, PAK5 and PAK6) only when they were in phosphorylated form (active). Keratinocytes of the basals stratum showed intense staining for phosphoPAKs 1/2,

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... the most superficial cells of the stratum spinosum and the surface layer showed moderate immunostaining for PAKs 4/5/6 phosphorylated in the epithelium adjacent to injured area. AC did not immunoexpress actives PAKs 1/2 and PAKs 4/5/6. LSSC did not immunoexpress phosphoPAKs 1/2, but some degenerating cells and cells in the necrotic area showed intense staining. Our results suggest that PAKs 1/2 not participate in the regulation of AC and LSCC pathogenesis, while PAKs 4/5/6 are involved in the regulation of cell death in LSCC.