Notch Signaling in Hepatocellular Carcinoma: Guilty in Association!

Notch signaling is a complex, highly conserved mechanism, originally discovered as critical regulator of cell fate determination during development in several tissues and organs.1,2 Activation of Notch may stimulate cells either to undergo a phenotypic switch or to maintain the original cell phenotype by preventing further differentiation,3 Notch is also involved in establishing organ-specific stem cell niches necessary for epithelial tissue homeostasis.3,4 The Notch system encompasses 4 genes encoding for different membrane receptors (Notch 1, 2, 3, and 4), which are activated by their binding to 5 ligands (Jagged-1, Jagged-2, and Delta-like 1, 3, and 4).