In other tumor entities, transcription of DR5 was shown to be activated by nuclear factor κB (NFκB), signal transducer and activator of transcription 1 (Stat1), p53 and Sp1 and repressed by Ying-Yang 1 (YY1).33 Although a Sp1-dependent regulation of DR5 was demonstrated in hepatocellular carcinoma,20, 34 breast cancer,35 colorectal cancer,36 and ovary cancer,37 a Notch1-mediated regulation of Sp1 and, consequently, the existence of a functional Notch1/Sp1/DR5 axis was so far unknown. This evidence concerns the gene TNFRSF10B and hepatocellular carcinoma.