Implications of NOTCH3 expression and signaling for cholangiocarcinogenesis

Question The NOTCH pathway is an evolutionary conserved signaling pathway, which has a pivotal role for physiological liver development and regeneration. Persistent hyperactivation of NOTCH signaling is a potential driver of liver cancer development and progression, particularly of the cholangiocarcinoma (CCA) subtype. However, compared to the well-studied NOTCH1 receptor, the role of NOTCH3 is poorly characterized. Similarly, the expression of NOTCH receptors in benign precursor lesions including biliary intraepithelial neoplasia (BillN) or intraductal papillary neoplasms of the bile duct (IPNB) was not yet investigated. Here, we elucidated the function of the atypical NOTCH3 receptor during cholangiocarcinogenesis.