IKKα regulates the stratification and differentiation of the epidermis: implications for skin cancer development

• DOI: 10.18632/oncotarget.12527
• Publication Date: 2016-10-08T15:08:10Z
• Authors: Josefa P. Alameda; Manuel Navarro; Ángel Ramírez; Angustias Page; Cristian Suárez-C...; Rodolfo Moreno-Ma...; Jesús M. Paramio; María del Carmen ...; Marcela Del Río; María Jesús Ferná...; Ana Bravo; María de los Llan...
• Keywords: skin; skin cancer; MMP9; IKKα; keratinocyte differentiation; Research Paper; 3. Good health

IKKα plays a mandatory role in keratinocyte differentiation and exerts an important task non-melanoma skin cancer development. However, it is not fully understood how these functions. To analyze detail the of epidermal stratification differentiation, we have generated tridimensional (3D) cultures human HaCaT keratinocytes fibroblasts fibrin gels, obtaining equivalents that comprise dermal compartments resembles both structure normal skin. We found expression must be strictly regulated epidermis, as alterations its levels lead to histological defects promote development malignant features. Specifically, augmented results increased proliferation clonogenicity keratinocytes, leads accelerated altered ability invasive growth, induction oncogenic proteins (Podoplanin, Snail, Cyclin D1) extracellular matrix proteolytic activity. All characteristics make overexpressing at higher risk developing cancer. Comparison genetic profile obtained by analysis microarrays RNA from genotypes supports above described findings.