For example, p53, a key transcription factor in senescence, has a repressive role in Nestin expression in liver progenitor cells, and loss of p53 (thus, Nestin upregulation) together with either WNT or NOTCH signaling promotes HCC or ICC development, respectively (Tschaharganeh et al. 2014). This evidence concerns the gene NES and intrahepatic cholangiocarcinoma.