NOTCH1 and liver cancer: In liver cancer stem cells (LCSCs), Notch1 functions downstream of Wnt/β-catenin signaling, relying on Wnt activation to NICD, yet paradoxically establishes a negative feedback loop suppressing β-catenin/TCF activity—demonstrated by increased β-catenin activity upon Notch1 knockdown and reduced transcriptional output following NICD overexpression.