Milea Timbergen

34 Figure 2. A schematic presentation of the Hedgehog signalling pathway and the drugs that interfere with this pathway in DTF. The graph depicts that inhibition of the Hedgehog pathway, by SMO inhibitors, works by blockage of Smoothened (SMO), a key regulator of downstream signaling by GLI transcription factors. The compound triparanol is known for inhibition of the cholesterol biosynthesis but can also interfere with Hedgehog signalling molecules including the Hedgehog ligand receptor Patched 1. The Notch signalling pathway in desmoid-type fibromatosis The Notch signalling pathway Notch signalling is essential for regulating cell-fate during tissue development and for managing cell proliferation, differentiation and survival, neurogenesis and homeostasis in adult tissues (reviewed by Artavanis-Tsakonas et al. 99 ). There are four mammalian transmembrane Notch receptors (Notch receptor family type 1-4; NOTCH 1-4). Each receptor is a Ca 2+ -stabilized heterodimer containing three domains: an extracellular (NECD), a transmembrane (NTMD) and an intracellular domain (NICD) (reviewed by Takebe et al. 100 ). These receptors can interact with ligands; members of the Delta-like (DLL1, DLL3 and DLL4), and the Jagged (JAG1 and JAG2) families. In case of ligand 2