HEY1 and cholangiocarcinoma: The Notch signaling pathway was variably activated in 5 CCA cell lines with high endogenous expression of ASPH as demonstrated by the generation of activated Notch1 ICN, high level expression of Jagged1 (JAG1) and upregulation of downstream target genes (e.g., HEY1 and HES1) (Fig 2A).