The role of pro- and anti-apoptotic signaling in skin cancer therapy
The intracellular balance between pro- and anti-apoptotic signaling pathways critically determines the fate of the cell. At the single cell level death receptor-induced apoptotsis is being antagonized by pro-survival pathways involving the transcription factor NFκB. While NFκB-dependent upregulation of anti-apoptotic genes was shown to inhibit death receptor-induced apoptosis, NFκB-dependent repression of anti-apoptotic genes was shown to enhance apoptosis induced by DNA damaging agents, including UVB. This paradox phenomenon is accompanied by an elevated release of TNF, which activates the TNF-RI in an autocrine fashion to additively enhance apoptosis. By using classical cell biological, molecular biological and also systems biological approaches we are aiming to decode sensitive nodal points in the apoptosis-NFκB- signaling network that might serve as cellular targets for improved and specific cancer treatment.
