NOTCH/HES5 signaling exhibits distinct roles in MYC- and AKT-driven liver carcinogenesis

Notch signaling plays a pivotal role in liver development and aberrant Notch signaling may lead to hepatocellular (HCC) or cholangiocellular carcinoma (CCA) development. Using whole exome sequencing of 54 human HCC samples, we discovered 19 somatic missense mutations in 15 different Notch pathway genes affecting 24.6% (14 of 57) of patients. Prediction of functional impact of these Notch pathway mutations revealed HES5-R31G to have high relevance. We used Hep3B cells infected with pTRIPZ expressing HES5 wildtype or HES5-R31G. Protein expression was induced with doxycycline (Dox).